Speciality
Spotlight

 




 


Oncology


 

 





Gynecologic
Malignancies

  

  • Rose
    PG, Bundy BN, Watkins EB, et al [Case Western Reserve
    Univ, Cleveland, Ohio; Roswell Park Cancer Inst,
    Buffalo, NY; Walter Reed Army Med Ctr, Washington, DC;
    et al]

    Concurrent
    Cisplatin-based Radiotherapy and Chemotheapy for Locally
    Advanced Cervical Cancer

    N
    Engl J Med 340: 1144-1153, 1999

     

    The
    study of 526 patients with locally advanced cervical
    cancer from stage IIB to IVA were randomized to cisplatin
    40mg/m2 per week for 6 weeks [ group I] or
    cisplatin 50mg/m2 followed by 5 fluorouracil
    4g/m2 given as 96 hour infusion on day 1 and
    day 29 and 6 weeks [group 2] or 3gm/m2 of
    oral hydroxyurea twice weekly for 6 weeks.

     

    Both
    groups [group 1 and group 2] who received cisplatin had
    a significantly higher rate of progression free
    survival.  The
    overall survival rate was significantly higher for
    patients in group I & Group II.

     

  • Keys
    HM, Bundy BN, Stehman FB, et al [Albany Med College, NY:
    Rosewell Park Cancer Inst, Buffalo, NY; Indiana Univ,
    Indianapolis; et al]

    Cisplatin,
    Radiation, and Adjuvant Hysterectomy Compared with
    Radiation and Adjuvant Hysterectomy for Bulky Stage IB
    Cervival Carcinoma

    N
    Engl J Med 340: 1154-1161, 1999

     


    The
    optimal treatment for stage IB cervival carcinoma is
    controversial.

     

    This
    study of 369 patients with biopsy proven stage IB
    cervical cancer without lymphadenopathy underwent
    radiotherapy and hysterectomy. These were randomized to
    weekly cisplat during underwent radiotherapy for 6 weeks
    or only radiotherapy. 3-6 weeks after radiotherapy
    extrafascial.

     

  • Morris
    M, Eifel PJ, Lu, J, et al [Univ of Texas MD Anderson
    Cancer Ctr, Houston; Radiation Therapy Oncology Group,
    Philadelphia; Washington Univ, St Louis; et al]

    Pelvic
    Radiation With Concurrent Chemotherapy Compared With
    Pelvic and Para-aortic Radiation for High-Risk Cervical
    Cancer

    N
    Engl J Med 340: 1137-1143, 1999

     

    Concomitant
    chemotherapy and radiotherapy has revealed increased
    survival in patients with locally advanced
    cervical cancer.

     

    This
    study of advanced cervical cancer stage IIB through IVA
    and a tumor diameter of at least 5 cm or involvement of
    pelvic nodes were assigned to pelvic radiotherapy [
    45Gy] and para-aortic
    lymph nodes or 45 GY of pelvic radiotherapy plus 2
    courses of 5 fluorouracil and cisplatin. The combined
    therapy had a higher reversible hematologic
    toxicity. The estimated cumulative rates of
    survival at 5 years for combined modality was 73%
    compare with 58% for radiotherapy alone.
    The rates of distant metastases and locoregional
    recurrence was also higher in patients treated with
    radiotherapy alone.

     

  • Sedlis
    A, Bundy BN, Rotman MZ, et al [ State Univ of New York,
    Brooklyn; Roswell Park Cancer Inst, Buffalo, NY; Bowman
    Gray School of Medicine, Winston-Salem NC; et al]

    A
    Randomized Trial of Pelvic Radiation Therapy Versus No
    Further Therapy in Selected Patients with Stage IB
    Carcinoma of the Cervix After Radical Hysterectomy and
    Pelvic Lymphadenectomy : A Gynecologic Oncology Group
    Study

    Gynecol
    Oncol 73: 177-183, 1999

     

    Stage
    I cervical cancer has a relatively favorable outlook.
    However, this study has brought out some risk factors
    within this favorable stage of cervical cancer.
    These risk factors are large tumor diameter, deep
    stormal invasion or presence of tumor in capillary
    lymphatic space. Adjuvant radiotherapy [i.e. after
    hysterectomy ] reduced the cancer recurrence among these
    patients with acceptable morbidity.

     

  • Knocke
    TH, Weitmann HD, Kucera H, et al [Univ of Vienna]

    Results
    of Primary and Adjuvant Radiotherapy in the Treatment of
    Mixed Mullerian Tumors of the Corpus Uteri

    Gynecol
    Oncol 73: 389-395, 1999

     


    The
    role of primary or adjuvant irradiation in the treatment
    of mixed mullerian tumor is undefined.

     

    The
    study of 63 patients with mixed mullerian
    tumor received primary radiotherapy in 3 patients
    and 50 received as adjuvant radiotherapy. This group of
    patients had improved local control and disease specific
    survival rates. The
    editor comments that the role of adjuvant radiation
    depends on the adequacy of surgical resection.

     

  • Papadimitriou
    CA, Sarris K, Moulopoulos LA, et al [ Univ of Athens,
    Greece; Aristotle Univ, Thessaloniki, Greece]

    Phase
    II Trial of Paclitaxel and Cisplatin in Metastatic and
    Recurrent Carcinoma of the Uterine Cervix

    J
    Clin Oncol 17: 761-766, 1999

     


    This
    study of 34  patients with
    metastatic or recurrent carcinoma of cervix were treated
    with injection paclitaxel 175 mg/m2 IV 3 hours infusion
    and IV cisplatinum 75 mg/m2 with granulocyte
    colony-stimulating factor, 47% of patient achieved an
    objective response. Neurotoxicity was the main adverse
    effect. The median duration of response is 5.5 month and overall survival 9
    months.

     

  • Tierney
    JF, Stewart LA, Parmar MKB [MRC Clinical Trials Unit,
    Cambridge England]

    Can
    the Published Data Tell Us About the Effectiveness of
    Neoadjuvant Chemotheapy for Locally Advanced Cancer of
    the Uterine Cervix?

    Eur
    J Cancer 35: 406-409, 1999

     


    This meta-analysis of all published reports of
    neoadjuvant chemotherapy in patients with locally
    advanced cancer of cervix did not have any conclusive
    evidence supporting the merits of an neoadjuvant
    chemotherapy.

     

  • Larson
    DM, Berg R, Shaw G, et al [Marshfield Clinic, Wis]

    Prognostic
    Significance of DNA Ploidy in Endometrial Cancer

    Gynecol
    Oncol 74: 356-360, 1999

     


    Endometrial
    cancer is a disease of obese and elderly and usually
    associated with medical problems thereby producing
    hindrances for an aggressive surgical approach.

     

    This
    study of 249 patients 
    with endometrial cancer underwent DNA ploidy
    assessment on patients staged surgically by standard
    protocol. Patients with aneuploid tumors had a
    significantly higher prevalence of pelvic node
    metastases and advanced surgical stage. It was also
    associated with increased risk of death from endometrial
    cancer.

     

  • Cook
    AM, Lodge N, Blake P [Royal Marsden Hosp, London]

    Stage
    IV Endometrial Carcinoma : A 10 Year Review of Patients

    Br
    J Radol 72: 485-488, 1999

     


    This study of 18 patients with stage IV endometrial
    carcinoma some underwent surgery, radiotherapy and some
    received chemotherapy and or hormonal therapy,
    progestogen. The overall median survival from the time of diagnosis was 12
    months or actuarial survival was 15%.
    The survival was similar with chemotherapy &
    hormonal therapy. The
    overall prognosis of stage IV is poor.

     

  • Barakat
    RR, Goldman NA, Patel DA, et al [ Mem Sloan-Kettering
    Cancer Ctr, New York, Mt Sinai Med Ctr, New York; Bronx
    Lebanon Hosp Ctr, New York]

    Pelvic
    Exenteration for Recurrent Endometrial Cancer

    Gynecol
    Oncol 75: 99-102, 1999

     


    This
    study of 44 patients with recurrent endometrial
    carcinoma underwent exenteration of
    which 80%
    had major postoperative
    complications
    and overall median survival was 10.2 months even
    though the longterm survival is only 20%.
    This approach remains the only potentially
    curative option for the few patients with central
    recurrence of endometrial cancer in whom surgical and
    radiation therapy has failed.

     

  • Bristow
    RE, Montz FJ, Lagasse LD, et al [ Univ of California Los
    Angeles; Johns Hopkins Med Institutions, Baltimore, Md]

    Survival
    Impact of Surgical Cytoreduction in Stage IV Epithelial
    Ovarian Cancer

    Gynecol
    Oncol 72: 278-287, 1999

     


    This study of 84 patients with stage IV ovarian
    cancer underwent debulking of extra hepatic disease. The impact of debulking in a subgroup of patients with liver
    metastasis revealed 
    optimal surgical debulking and good performance
    status were good prognostic factors and leading to
    significant survival advantage in this subgroup of
    patients.

     

  • Duska
    LR, Chang Y, Flynn CE, et al [Massachusetts Gen Hosp,
    Boston]

    Epithelial
    Ovarian Carcinoma in the Reproductive Age Group

    Cancer
    85: 2623-2629, 1999

     


    This
    study of women under 40 years of age with epithelial
    ovarian cancer was retrospectively analyzed to ascertain
    whether the patient age and tumor grade are prognostic
    factors for survival. Only tumor grade [with borderline
    tumors ] and stage were significant predictors of
    survival in multivariate analysis. Of the 92 epithelial tumors 50% had borderline tumors. The 5 year
    survival rate for patients with advanced epithelial
    ovarian carcinoma was 22.9%. Borderline tumors have an
    good prognosis
    with
    possibility of preserving fertility after cancer
    treatment which is mostly a surgical option.

     

  • Judson
    PL, Watson JM, Gehrig PA, et al [ Univ of North
    Carolina, Chjapel Hill]

    Cisplatin
    Inhibits Paclitaxel –Induced Apoptosis in Cisplatin-resistant
    Ovarian Cancer Cell Lines : Possible Explanation for
    Failure of Combination Therapy

    Cancer
    Res 59: 2425-2432, 1999

     


    This
    study of the human ovarian cancer cells are treated with
    cisplatin alone, paclitaxel alone or both agents and the
    percentage of cell survival was noted.

     

    Cisplatin
    appears to inhibit paclitaxel’s efficacy in cisplatin
    cell lines, blocking paclitaxel-induced apoptosis. Thus,
    paclitaxel is to be used as second line regimen in
    patients with cisplatin paclitaxel resistant ovarian
    cancer as per this in vitro study. The editor comments
    that this explains the  response in some patients to docetaxel who
    are labeled to be resistant to paclitaxel.

     

  • Shinozuka
    T, Miyamoto T, Muramatsu T, et al [ Tokai Univ, Isehara,
    Kanagawa, Japan]

    High
    Dose Chemotherapy With Autologous Stem Cell Support in
    the Treatment of Patients With Ovarian Carcinoma: Long
    Term Results for 105 Patients

    Cancer
    85: 1555-1564, 1999

     


    This study is of patients of with ovarian carcinoma who had
    received  platinum
    therapy followed by debulking procedures and then high
    dose chemotherapy with stem cell support. The patient
    with advanced ovarian cancer who have small volume
    disease, platinum sensitivity and chemosensitive tumors
    prior to high dose chemotherapy had the best long term
    survival. The editor comments that this modality should
    not be used outside a phase III trial until we have data
    demonstrating its advantage over standard therapy.

       
          
                         

  • Rose
    PG, Fusco N, Fluellen L, et al [ Univ MacDonald Womens
    Hosp/Univ Hosp of Cleveland Ohio Ireland Cancer Ctr,
    Cleveland, Ohio; Case Western Reserve Univ, Cleveland,
    Ohio ]

    Second-line Therapy with Paclitaxel and Carboplatin
    for Recurrent Disease Following First-Line Therapy with
    Paclitaxel and Platinum in Ovarian or Peritoneal
    Carcinoma


    J Clin Oncol 16: 1494-1497, 1998

      

    Paclitaxel carboplatinum has now formed the mainstay
    therapy for patients with advence ovarian cancer. This
    studdy of 25 patients with a recurrence in ovarian
    cancer six months after complete response to paclitaxel
    and carboplatin were retreated with paclitaxel as
    continuous infusion with carboplatin. Retreatment with
    paclitaxel and carboplatin produced a response rate of
    91%. Sixty percent of the patients had a recurrence
    after repeat treatment at a median of 9 months.

      

    The editor comments that although these results are
    impressive in select group of patients with recurrence
    of ovarian cancer, these results could be possible by
    single agent such as paclitaxel or platinum and there by
    decreasing the side effects of palliative therapy.

      

  • Stewart LA, for the Advanced Ovarian Cancer Trialists’ Group [Medical Research Council Cancer Trials Office, Cambridge, England]

    Chemotherapy in Advanced Ovarian Cancer : Four Systematic Meta-analyses of Individual Patient Data from 37 Randomized Trials

    Br J Cancer 78: 1479-1487, 1998

      

    This large study includes 5667 patients from thirty seven randomized controlled trials. The analysis concluded platinum -based chemotherapy is superior to non-platinum therapy & trend favoring combination with platinum. Cisplatin and carboplatin had equal efficacy.

        

  • Bridgewater JA, Nelstrop AE, Rustin GJS, et al [ Mount Vernon Centre for Cancer Treatment, Middlesex, England; Royal Marsden Hosp, London; Univ of Mississipi, Jackson; et al]

    Comparison of Standard and CA-125 Response Criteria in Patients with Epithelial Ovarian Cancer Treated with Platinum or Paclitaxel

    J Clin Oncol 17 : 501-508, 1999

       

    This study evaluated CA-125 as a measure of response in ovarian cancer patients treated with paclitaxel. A
    precise 50-75% CA-125 response criterion has been shown as a sensitive indicator comparable to standard response criteria. However, 1 in 5 patients who are non responders using CA-125 criteria may be undertreated and CT scans may be of value in these patients management.

      

  • Schwartz PE, Rutherford TJ, Chambers JT, et al [Yale Univ, New Haven, Conn: Diagnostic Oncology CRO, Stratford, Conn]

    Neoadjuvant Chemotherapy for Advanced Ovarian Cancer: Long-term Survival

    Gynecol Oncol 72: 93-99, 1999

      

    This study of 785 patients with advanced ovarian carcinoma compared neoadjuvant chemotherapy [i.e. prior to surgery] with primary debulking surgery. In some patients laparoscopy was used to identify patients requiring neoadjuvant chemotherapy. In this retrospective study better crude survival i.e. 42% vs. 26% was achieved for advanced ovarian carcinoma patients undergoing primary chemotherapy rather than primary debulking . In addition morbidity and mortality of surgery are decreased when performed after chemotherapy induced debulking. A prospective randomized study is required to substantiate the above statement.

        

  • Gershenson DM, Silva EG, Levy L, et al [Univ of Texas MD Anderson Cancer Ctr, Houston]

    Ovarian Serous Borderline Tumors with Invasive Peritoneal Implants

    Cancer 82: 1096-1103, 1998

       

    Borderline tumor with peritoneal implants when diagnosed following surgery has no accepted standard postoperative therapy.

     

    This study from M.D. Anderson consisting of 30 women with primary serous borderline tumor with invasive peritonal implants used post operative chemotherapy. Most of the patients received platinum based others melphalan chemotherapy. Time to progression was significantly longer for those patients with no macroscopic residual disease, after initial surgery, and platinum based therapy was associated with shorter progression free survival which is contrary to the management of classic epithelial carcinoma of ovary.

        

  • Parmar
    MKB, for the ICON Collaborators [Istituto de Richerche, Milano, Italy]

    ICON2 : Randomized Trial of Single-Agent Carboplatin Against Three Drug Combination of CAP [ Cyclophosphamide, Doxorubicin, and Cisplatin] in Women with Ovarian Cancer

    Lancet 352: 1571- 176, 1998

       

    This study of 1256 patients compared cyclophosphamide, adriamycin and cisplatin
    (CAP) to single agent carboplatinum, survival curves showed no difference between CAP and carboplatin. The toxicity association with CAP was greater than from single agent carboplatin. The editor comments that as per the conclusion of the author
    carboplatin can be considered appropriate standard treatment for women with advanced ovarian cancer. This would ignore the two large studies by Gynecologic Oncology Group and by the European Organization for Research in Cancer Therapy which revealed paclitaxel plus cisplatin to improve survival.

       

  • Bookman MA, Malmstrom H Bolis G, et al [Fox Chase Cancer Ctr, Phildelphia; Smithkline Beecham Pharmaceuticals, Collegeville, Pa; Texas Oncology Physician Assoc, Dallas; et al]

    Topotecan for the Treatment of Advanced Epithelial Ovarian Cancer : An Open-Label Phase II Study in Patients Treated after Prior Chemotherapy That Contained Cisplatin or Carboplatin and Paclitaxel

    J Clin Oncol 16: 3345-332, 1998

       

    Paclitaxel and platinum have become a standard of care for advanced ovarian cancer. This makes second line or salvage therapy difficult, following a recurrence of ovarian cancer. This study of 139 patients with recurrent ovarian cancer and had earlier received paclitaxel and platinum received topotecan as second line.

      

    The overall response rate was 13.7% and only 12.4% for platinum resistant patients. It was associated with grade IV neutropenia in 82% of courses. The editor comments in view of such modest activity in recurrent ovarian cancer, topotecan may be considered in previously untreated patients along with other potent chemotherapy agents used in ovarian cancer.

         

  • Gore M, for the London Gynaecological Oncology Group [Royal Marsden Natl Health Service Trust, London]

    Randomized Trial of Dose-Intensity with Single-Agent Carboplatin in Patients With Epithelial Ovarian Cancer

    J Clin Oncol 16: 2426-2434, 1998

       

    Platinum drug are considered essential as first line chemotherapeutic agents in epithelial ovarian cancer & whether dose escalation of these drug would increase the survival. This study of 227 patients were assigned to AUC of 6 or 12 for 6 courses or 4 courses respectively. The progression free and overall survival did not differ
    between the two treatment groups although significant hematologic toxicity was observed in higher dosage arm. The editor comments that by increasing the dose of platinum 5-6 times the standard dose would require peripheral stem cell transfusion and whether this would be advantageous will require further randomized study for patients with advanced ovarian cancer.

        

  • Tai Y-T Lee S, Niloff E, et al [Dana-Farber Cancer Inst, Boston; Hrvard Med School, Boston]

    BAX Protein Expression and Clinical Outcome in Epithelial Ovarian Cancer

    J Clin Oncol 16: 2583-2590, 1998

      

    In vitro studies have shown that pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro.

       

    Forty five newly diagnosed patients with ovarian cancer were analyzed for BAX expression. The tumor tissue with high BAX expression had an improved clinical outcomes suggestive of an intact apoptotic pathway leading to chemo responsiveness of ovarian cancer to paclitaxel.

       

  • Markman M, Brady MF, Spirtos NM, et al [Cleveland Clinic Found, Ohio; Roswell Park Cancer Inst, Buffalo NY: Women’s Cancer Ctr of Northern California , Palo Alto; et al]

    Phase II Trial of Intraperitoneal Paclitaxel in Carcinoma of the Ovary, Tube and Peritoneum: A Gynecologic Oncology Group Study

    J Clin Oncol 16: 2620-2624, 1998

      

    This study of 76 patients with recurrent ovarian and fallopian tube cancer or primary carcinoma of the peritoneum were evaluated. The largest residual disease was 0.5 cm or less in maximum diameter. These patients received intra peritoneal paclitaxel.

     

    61% of the patients achieved complete response in patients with microscopic disease in contrast the response rate was only 3% with macroscopic disease moderate abdominal pain and neutropenia were the frequent side effects.

        

  • Brader KR, Morris M, Levenback C, et al [ Univ of Texas, Houston]

    Chemotherapy for Cervical Carcinoma : Factors Determining Response and Implications for Clinical Trial Design

    J Clin Oncol 16: 1879-1884, 1998

       

    The prognostic factors of the patients with cervical squamous cancer for response to palliative chemotherapy were studied in 190 chemonative patients. Older patients were more likely to respond and in patients in whom the recurrence is outside the irradiated field have a favourable response rate 25.2% compared to 5.3% for those with recurrence in the irradiated field. The editor comments that poor response to chemotherapy in such patients could be the poor vasculature due to previous surgery or radiation.

          

  • Cheng W-F, Chen C-A, Lee C-N, et al [Natl Taiwan Univ Hosp, Taipei]

    Vascular Endothelial Growth Factor in Cervical Carcinoma

    Obstet Gynecol 93: 761-765, 1999

      

    The expression of vascular endothelial growth factor [VEGF] is an angiogenesis stimulating cyto kene which is a forerunner of growth and metastasis in solid tumor.

      

    This study of 104 consecutive women with cervical cancer, VEGF levels were determined in cervical tissue specimen with clinical stage IB through IIA and from 30 consecutive women with benign disease. High VEGF levels were found in tumours larger than 4 cm and deep stromal invasion, lymphovascular emboli parametrial invasion or pelvic lymph node meastasis VEGF correlated with tumor size.

           

  • Obermair A, Tempfer C, Wasicky R, et al [Univ Hosp of Vienna]

    Prognostic Significance of Tumor Angiogenesis in Endometrial Cancer

    Obstet Gynecol 93: 367-371, 1999

      

    In this study of endometrial cancer specimens were stained with CD34 antigen and microvessels counted. Overall survival and microvessal density were compared. After adjusting for disease stage and histologic grade, microvessel density was an independent predictor of survival. The growth and spread of endometrial cancer depends on angiogenesis.

         

  • Alvarez AA, Krigman HR, Whitaker RS, et al [Duke Univ, Durham, NC]

    The Prognostic Significance of Angiogenesis in Epithelial Ovarian Carcinoma

    Clin Cancer Res 5: 587-591, 1999

      

    This study of 88 patients with ovarian cancer underwent staining, tissue section with antihuman endothelial cell antibodies to von Willebrand factor and CD31, tp determine the degree of
    angiogenesis. 

         

    The estimated median survival was 79 years for women with a microvessel density count of more than 10 or less and 2.7 years for women with less than 10. The degree of neovascularization was significantly and negatively related to the rate of survival 

    after adjusting for stage. Patients with low angiogenic counts have a significantly improved rate of survival.

         

  • Menon U, Talaat A, Jeyarajah AR, et al [St Bartholomew’s and Royal London School of Medicine and Dentistry; Harvard Med School, Boston]

    Ultrasound Assessment of Ovarian Cancer Risk in Postmenopausal Women With CA125 Elevation

    Br J Cancer 80: 1644-1647, 1999

         

    This study of 22,000 postmenopausal women, 45 years or older screened for CA125. Women with CA 125 levels 30 U/ml or higher underwent ultrasound [US].
    Those with normal architecture on US had cumulative risk of ovarian cancer to be 0.15% similar to general population. Whereas those with abnormal ovarian architecture had cumulation risk of 24%. This group merits aggressive evaluation for ovarian cancer.

         

  • Du Bois A, Luck HJ, Bauknecht T, et al [Frauenklinik St Vincentius Hrankenhaus, Karlsruhe, Germany; Frauenklinik Medizinische Hochschule,Hannover, Germany; Universitatsfrauenklinik, Freiburg, Germany; et al]

    First-line Chemotherapy with Epirubicin, Paclitaxel, and Carboplatin for Advanced Ovarian Cancer : A Phase I/II Study of the Arbeitsgemeinschaft Gynakologische Okologie Ovarian Cancer Study Group

    J Clin Oncol 17: 46-51, 1999

     

    This study is to evaluate the maximum tolerated dose, safety, and feasibility of a 3-drug combination containing epirubicin with carboplatin and paclitaxel in previously untreated ovarian cancer.

      

    The maximum tolerated dose of epirubicin 60mg/m2 followed by paclitaxel 175 mg/m2 and carboplatin AUC5. Four of the seven achieved a complete remission 1 had partial response and 1 had progression and 10 of the fourteen with nonmeasurable disease had no evidence of disease after completion of treatment. This 3 drug combination had sufficient activity to warrant prospective randomized trials comparing paclitaxel carboplatin in previously untreated patients.

         

  • Hammond LA, Eckardt JR, Ganapathi R, et al [ Cancer Therapy and Research Ctr, San Antonio, Tex; Univ of Tex Health Science Ctr, San Antonio; Audie Murphy VA Hosp, San Antonio, Tex; et al]

    A Phase I and Translational Study of Sequential Administration of the Topoisomerase I and II Inhibitors Topotecan and Etoposide

    Clin Cancer Res 4: 1459-1467, 1998

        

    The main effect of topoisomerase I, topotecan [TPT] followed by topo II inhibitor such etoposide was assessed in patients with solid malignancies. As the main effect of topo1 and topo II inhibitors are two major classes of enzymes involved in regulating DNA topology in the cell. Although some clinical activity was observed. There was substantial toxicity and hence sequential treatment with these 2 agents would not be superior to either agents alone.

         

  • Parslov Michael, Lidegaard Ojvind, Klintorp Soren, et al, Copenhagen, Denmark

    Risk factors among young women with endometrial cancer: A Danish case-control study.

    Am J Obstet Gynecol 2000; 182: 23-29

      

    This study was undertaken to identify and quantify risk factors for endometrial cancer among young women.

      

    Endometrial cancer is a rare disease among premenopausal women. Seven percent of endometrial cancer occurs in women <50 years old. In the same age group about 300 curettage procedures and an equal number of endometrial biopsies are performed for every single diagnosis of endometrial cancer. When the physical complications attendant with these invasive procedures and the socioeconomic consequences of curettage as a screening procedure are considered, the question arises as to whether it is appropriate to carry out this number of intrauterine procedures in fertile women to find so few cases of endometrial malignancy.

       

    Several studies have identified risk factors of endometrial cancer among older women, such as overweight status, estrogen replacement therapy, nulliparity, infertility, diabetes mellitus, and hypertension. However, these risk factors are not necessarily relevant for endometrial cancer among young women.

      

    Hence this study was undertaken and findings were controlling for confounding influence from the other determinants revealed the following variables to be independent risk factors: family history of endometrial cancer, parity, age at first birth, number of induced abortions, use of oral contraceptives, and use of hormone replacement therapy.

      

    Women with a family history of endometrial cancer (mother or sister) had an odd ratio of endometrial cancer of 2.1 (95% confidence interval).

       

    Family predisposition: Family history of endometrial cancer in a first-degree relative (mother or sister) is a well-documented risk factor for endometrial cancer among both premenopausal and postmenopausal women, with odds ratios between 1.5 and 2.8. This relationship was confirmed by our data. It should be noted that the estimated odds ratio of 2.1 represents the impact of family predisposition after body mass index is controlled for. Thus the increased risk was caused by genetic circumstances other than adiposity.

      

    Diabetes and hypertension: In this study no significant association emerged between endometrial cancer and diabetes. Hypertension was not an independent risk factor.

        

    Cigarette smoking : In this study authors were not able to demonstrate an independent effect of smoking and anti-estrogenic effect of smoking.

      

    All studies have demonstrated a protective effect of cigarette smoking on the risk of development of endometrial cancer among postmenopausal women. It is remarkable that the protective influence of cigarette smoking has not been apparent in several studies on premenopausal women with endometrial cancer.

      

    Education : After adjustment for all variables, authors could not retrieve an association with years of schooling, which is a reliable indicator of social class.

      

    Etiologic fraction : With a mother or sister who had endometrial cancer the risk of development of endometrial cancer was increased by a factor of 2. Hormone replacement therapy increased risk by a factor of 3 but only about 2% of premenopausal women receive hormone replacement therapy. Consequently, the etiologic fraction of hormone replacement therapy was 4%. Oral contraceptive use of >1year; ³ 2 term pregnancies, age ³ 30 years when giving birth at first time, and a history of incomplete pregnancies are all conditions that decreased the risk of development of endometrial cancer.

        

    In conclusion, a number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women. These are family history of endometrial cancer, reproductive history, hormone replacement therapy, and the use of oral contraceptives.

      

    Increasing number of births reduced the risk of endometrial cancer. If all women gave birth ³ 2 times, about 40% of endometrial cancer in the premenopausal age group could be eliminated.

         

  • Gordon AN, Fleagle TJ, Guthrie D, et al 

    Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin (PLD) Versus Topotecan (TN)

    J Clin Oncol 2001, 19: 3312-3322 

    Literature Alert – Current Oncology Reports Vol. 3(6) November 2001 Pg. 456

           

    This phase
    III randomized multicenter study of 474 patients of ovarian carcinoma who had recurrence. These were stratified for platinum sensitive or refractory disease and for presence or absence of bulky disease.

          

    The patients were randomized to PLD or TN. In the overall analysis, the overall survival, progression free survival and response rates were similar. However, subgroup analysis PLD was superior to TN for both PFS and overall survival in patients with platinum sensitive
    relapse.

           

    In platinum resistant patients TN had a non statistically significant trend toward improved survival. No differences were seen for patients with or without bulky recurrent
    disease.

         


 

 



 

 

Speciality Spotlight

 

 

Gynecologic Malignancies
  

  • Rose PG, Bundy BN, Watkins EB, et al [Case Western Reserve Univ, Cleveland, Ohio; Roswell Park Cancer Inst, Buffalo, NY; Walter Reed Army Med Ctr, Washington, DC; et al]
    Concurrent Cisplatin-based Radiotherapy and Chemotheapy for Locally Advanced Cervical Cancer
    N Engl J Med 340: 1144-1153, 1999
     
    The study of 526 patients with locally advanced cervical cancer from stage IIB to IVA were randomized to cisplatin 40mg/m2 per week for 6 weeks [ group I] or cisplatin 50mg/m2 followed by 5 fluorouracil 4g/m2 given as 96 hour infusion on day 1 and day 29 and 6 weeks [group 2] or 3gm/m2 of oral hydroxyurea twice weekly for 6 weeks.
     
    Both groups [group 1 and group 2] who received cisplatin had a significantly higher rate of progression free survival.  The overall survival rate was significantly higher for patients in group I & Group II.
     

  • Keys HM, Bundy BN, Stehman FB, et al [Albany Med College, NY: Rosewell Park Cancer Inst, Buffalo, NY; Indiana Univ, Indianapolis; et al]
    Cisplatin, Radiation, and Adjuvant Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bulky Stage IB Cervival Carcinoma
    N Engl J Med 340: 1154-1161, 1999
     
    The optimal treatment for stage IB cervival carcinoma is controversial.
     
    This study of 369 patients with biopsy proven stage IB cervical cancer without lymphadenopathy underwent radiotherapy and hysterectomy. These were randomized to weekly cisplat during underwent radiotherapy for 6 weeks or only radiotherapy. 3-6 weeks after radiotherapy extrafascial.
     

  • Morris M, Eifel PJ, Lu, J, et al [Univ of Texas MD Anderson Cancer Ctr, Houston; Radiation Therapy Oncology Group, Philadelphia; Washington Univ, St Louis; et al]
    Pelvic Radiation With Concurrent Chemotherapy Compared With Pelvic and Para-aortic Radiation for High-Risk Cervical Cancer
    N Engl J Med 340: 1137-1143, 1999
     
    Concomitant chemotherapy and radiotherapy has revealed increased survival in patients with locally advanced cervical cancer.
     
    This study of advanced cervical cancer stage IIB through IVA and a tumor diameter of at least 5 cm or involvement of pelvic nodes were assigned to pelvic radiotherapy [ 45Gy] and para-aortic lymph nodes or 45 GY of pelvic radiotherapy plus 2 courses of 5 fluorouracil and cisplatin. The combined therapy had a higher reversible hematologic toxicity. The estimated cumulative rates of survival at 5 years for combined modality was 73% compare with 58% for radiotherapy alone. The rates of distant metastases and locoregional recurrence was also higher in patients treated with radiotherapy alone.
     

  • Sedlis A, Bundy BN, Rotman MZ, et al [ State Univ of New York, Brooklyn; Roswell Park Cancer Inst, Buffalo, NY; Bowman Gray School of Medicine, Winston-Salem NC; et al]
    A Randomized Trial of Pelvic Radiation Therapy Versus No Further Therapy in Selected Patients with Stage IB Carcinoma of the Cervix After Radical Hysterectomy and Pelvic Lymphadenectomy : A Gynecologic Oncology Group Study
    Gynecol Oncol 73: 177-183, 1999
     
    Stage I cervical cancer has a relatively favorable outlook. However, this study has brought out some risk factors within this favorable stage of cervical cancer. These risk factors are large tumor diameter, deep stormal invasion or presence of tumor in capillary lymphatic space. Adjuvant radiotherapy [i.e. after hysterectomy ] reduced the cancer recurrence among these patients with acceptable morbidity.
     

  • Knocke TH, Weitmann HD, Kucera H, et al [Univ of Vienna]
    Results of Primary and Adjuvant Radiotherapy in the Treatment of Mixed Mullerian Tumors of the Corpus Uteri
    Gynecol Oncol 73: 389-395, 1999
     
    The role of primary or adjuvant irradiation in the treatment of mixed mullerian tumor is undefined.
     
    The study of 63 patients with mixed mullerian tumor received primary radiotherapy in 3 patients and 50 received as adjuvant radiotherapy. This group of patients had improved local control and disease specific survival rates. The editor comments that the role of adjuvant radiation depends on the adequacy of surgical resection.
     

  • Papadimitriou CA, Sarris K, Moulopoulos LA, et al [ Univ of Athens, Greece; Aristotle Univ, Thessaloniki, Greece]
    Phase II Trial of Paclitaxel and Cisplatin in Metastatic and Recurrent Carcinoma of the Uterine Cervix
    J Clin Oncol 17: 761-766, 1999
     
    This study of 34  patients with metastatic or recurrent carcinoma of cervix were treated with injection paclitaxel 175 mg/m2 IV 3 hours infusion and IV cisplatinum 75 mg/m2 with granulocyte colony-stimulating factor, 47% of patient achieved an objective response. Neurotoxicity was the main adverse effect. The median duration of response is 5.5 month and overall survival 9 months.
     

  • Tierney JF, Stewart LA, Parmar MKB [MRC Clinical Trials Unit, Cambridge England]
    Can the Published Data Tell Us About the Effectiveness of Neoadjuvant Chemotheapy for Locally Advanced Cancer of the Uterine Cervix?
    Eur J Cancer 35: 406-409, 1999
     
    This meta-analysis of all published reports of neoadjuvant chemotherapy in patients with locally advanced cancer of cervix did not have any conclusive evidence supporting the merits of an neoadjuvant chemotherapy.
     

  • Larson DM, Berg R, Shaw G, et al [Marshfield Clinic, Wis]
    Prognostic Significance of DNA Ploidy in Endometrial Cancer
    Gynecol Oncol 74: 356-360, 1999
     
    Endometrial cancer is a disease of obese and elderly and usually associated with medical problems thereby producing hindrances for an aggressive surgical approach.
     
    This study of 249 patients  with endometrial cancer underwent DNA ploidy assessment on patients staged surgically by standard protocol. Patients with aneuploid tumors had a significantly higher prevalence of pelvic node metastases and advanced surgical stage. It was also associated with increased risk of death from endometrial cancer.
     

  • Cook AM, Lodge N, Blake P [Royal Marsden Hosp, London]
    Stage IV Endometrial Carcinoma : A 10 Year Review of Patients
    Br J Radol 72: 485-488, 1999
     
    This study of 18 patients with stage IV endometrial carcinoma some underwent surgery, radiotherapy and some received chemotherapy and or hormonal therapy, progestogen. The overall median survival from the time of diagnosis was 12 months or actuarial survival was 15%. The survival was similar with chemotherapy & hormonal therapy. The overall prognosis of stage IV is poor.
     

  • Barakat RR, Goldman NA, Patel DA, et al [ Mem Sloan-Kettering Cancer Ctr, New York, Mt Sinai Med Ctr, New York; Bronx Lebanon Hosp Ctr, New York]
    Pelvic Exenteration for Recurrent Endometrial Cancer
    Gynecol Oncol 75: 99-102, 1999
     
    This study of 44 patients with recurrent endometrial carcinoma underwent exenteration of which 80% had major postoperative complications and overall median survival was 10.2 months even though the longterm survival is only 20%. This approach remains the only potentially curative option for the few patients with central recurrence of endometrial cancer in whom surgical and radiation therapy has failed.
     

  • Bristow RE, Montz FJ, Lagasse LD, et al [ Univ of California Los Angeles; Johns Hopkins Med Institutions, Baltimore, Md]
    Survival Impact of Surgical Cytoreduction in Stage IV Epithelial Ovarian Cancer
    Gynecol Oncol 72: 278-287, 1999
     
    This study of 84 patients with stage IV ovarian cancer underwent debulking of extra hepatic disease. The impact of debulking in a subgroup of patients with liver metastasis revealed  optimal surgical debulking and good performance status were good prognostic factors and leading to significant survival advantage in this subgroup of patients.
     

  • Duska LR, Chang Y, Flynn CE, et al [Massachusetts Gen Hosp, Boston]
    Epithelial Ovarian Carcinoma in the Reproductive Age Group
    Cancer 85: 2623-2629, 1999
     
    This study of women under 40 years of age with epithelial ovarian cancer was retrospectively analyzed to ascertain whether the patient age and tumor grade are prognostic factors for survival. Only tumor grade [with borderline tumors ] and stage were significant predictors of survival in multivariate analysis. Of the 92 epithelial tumors 50% had borderline tumors. The 5 year survival rate for patients with advanced epithelial ovarian carcinoma was 22.9%. Borderline tumors have an good prognosis with possibility of preserving fertility after cancer treatment which is mostly a surgical option.
     

  • Judson PL, Watson JM, Gehrig PA, et al [ Univ of North Carolina, Chjapel Hill]
    Cisplatin Inhibits Paclitaxel –Induced Apoptosis in Cisplatin-resistant Ovarian Cancer Cell Lines : Possible Explanation for Failure of Combination Therapy
    Cancer Res 59: 2425-2432, 1999
     
    This study of the human ovarian cancer cells are treated with cisplatin alone, paclitaxel alone or both agents and the percentage of cell survival was noted.
     
    Cisplatin appears to inhibit paclitaxel’s efficacy in cisplatin cell lines, blocking paclitaxel-induced apoptosis. Thus, paclitaxel is to be used as second line regimen in patients with cisplatin paclitaxel resistant ovarian cancer as per this in vitro study. The editor comments that this explains the  response in some patients to docetaxel who are labeled to be resistant to paclitaxel.
     

  • Shinozuka T, Miyamoto T, Muramatsu T, et al [ Tokai Univ, Isehara, Kanagawa, Japan]
    High Dose Chemotherapy With Autologous Stem Cell Support in the Treatment of Patients With Ovarian Carcinoma: Long Term Results for 105 Patients
    Cancer 85: 1555-1564, 1999
     
    This study is of patients of with ovarian carcinoma who had received  platinum therapy followed by debulking procedures and then high dose chemotherapy with stem cell support. The patient with advanced ovarian cancer who have small volume disease, platinum sensitivity and chemosensitive tumors prior to high dose chemotherapy had the best long term survival. The editor comments that this modality should not be used outside a phase III trial until we have data demonstrating its advantage over standard therapy.
       
                                

  • Rose PG, Fusco N, Fluellen L, et al [ Univ MacDonald Womens Hosp/Univ Hosp of Cleveland Ohio Ireland Cancer Ctr, Cleveland, Ohio; Case Western Reserve Univ, Cleveland, Ohio ]
    Second-line Therapy with Paclitaxel and Carboplatin for Recurrent Disease Following First-Line Therapy with Paclitaxel and Platinum in Ovarian or Peritoneal Carcinoma
    J Clin Oncol 16: 1494-1497, 1998
      
    Paclitaxel carboplatinum has now formed the mainstay therapy for patients with advence ovarian cancer. This studdy of 25 patients with a recurrence in ovarian cancer six months after complete response to paclitaxel and carboplatin were retreated with paclitaxel as continuous infusion with carboplatin. Retreatment with paclitaxel and carboplatin produced a response rate of 91%. Sixty percent of the patients had a recurrence after repeat treatment at a median of 9 months.
      
    The editor comments that although these results are impressive in select group of patients with recurrence of ovarian cancer, these results could be possible by single agent such as paclitaxel or platinum and there by decreasing the side effects of palliative therapy.
      

  • Stewart LA, for the Advanced Ovarian Cancer Trialists’ Group [Medical Research Council Cancer Trials Office, Cambridge, England]
    Chemotherapy in Advanced Ovarian Cancer : Four Systematic Meta-analyses of Individual Patient Data from 37 Randomized Trials
    Br J Cancer 78: 1479-1487, 1998
      
    This large study includes 5667 patients from thirty seven randomized controlled trials. The analysis concluded platinum -based chemotherapy is superior to non-platinum therapy & trend favoring combination with platinum. Cisplatin and carboplatin had equal efficacy.
        

  • Bridgewater JA, Nelstrop AE, Rustin GJS, et al [ Mount Vernon Centre for Cancer Treatment, Middlesex, England; Royal Marsden Hosp, London; Univ of Mississipi, Jackson; et al]
    Comparison of Standard and CA-125 Response Criteria in Patients with Epithelial Ovarian Cancer Treated with Platinum or Paclitaxel
    J Clin Oncol 17 : 501-508, 1999
       
    This study evaluated CA-125 as a measure of response in ovarian cancer patients treated with paclitaxel. A precise 50-75% CA-125 response criterion has been shown as a sensitive indicator comparable to standard response criteria. However, 1 in 5 patients who are non responders using CA-125 criteria may be undertreated and CT scans may be of value in these patients management.
      

  • Schwartz PE, Rutherford TJ, Chambers JT, et al [Yale Univ, New Haven, Conn: Diagnostic Oncology CRO, Stratford, Conn]
    Neoadjuvant Chemotherapy for Advanced Ovarian Cancer: Long-term Survival
    Gynecol Oncol 72: 93-99, 1999
      
    This study of 785 patients with advanced ovarian carcinoma compared neoadjuvant chemotherapy [i.e. prior to surgery] with primary debulking surgery. In some patients laparoscopy was used to identify patients requiring neoadjuvant chemotherapy. In this retrospective study better crude survival i.e. 42% vs. 26% was achieved for advanced ovarian carcinoma patients undergoing primary chemotherapy rather than primary debulking . In addition morbidity and mortality of surgery are decreased when performed after chemotherapy induced debulking. A prospective randomized study is required to substantiate the above statement.
        

  • Gershenson DM, Silva EG, Levy L, et al [Univ of Texas MD Anderson Cancer Ctr, Houston]
    Ovarian Serous Borderline Tumors with Invasive Peritoneal Implants
    Cancer 82: 1096-1103, 1998
       
    Borderline tumor with peritoneal implants when diagnosed following surgery has no accepted standard postoperative therapy.
     
    This study from M.D. Anderson consisting of 30 women with primary serous borderline tumor with invasive peritonal implants used post operative chemotherapy. Most of the patients received platinum based others melphalan chemotherapy. Time to progression was significantly longer for those patients with no macroscopic residual disease, after initial surgery, and platinum based therapy was associated with shorter progression free survival which is contrary to the management of classic epithelial carcinoma of ovary.
        

  • Parmar MKB, for the ICON Collaborators [Istituto de Richerche, Milano, Italy]
    ICON2 : Randomized Trial of Single-Agent Carboplatin Against Three Drug Combination of CAP [ Cyclophosphamide, Doxorubicin, and Cisplatin] in Women with Ovarian Cancer
    Lancet 352: 1571- 176, 1998
       
    This study of 1256 patients compared cyclophosphamide, adriamycin and cisplatin (CAP) to single agent carboplatinum, survival curves showed no difference between CAP and carboplatin. The toxicity association with CAP was greater than from single agent carboplatin. The editor comments that as per the conclusion of the author carboplatin can be considered appropriate standard treatment for women with advanced ovarian cancer. This would ignore the two large studies by Gynecologic Oncology Group and by the European Organization for Research in Cancer Therapy which revealed paclitaxel plus cisplatin to improve survival.
       

  • Bookman MA, Malmstrom H Bolis G, et al [Fox Chase Cancer Ctr, Phildelphia; Smithkline Beecham Pharmaceuticals, Collegeville, Pa; Texas Oncology Physician Assoc, Dallas; et al]
    Topotecan for the Treatment of Advanced Epithelial Ovarian Cancer : An Open-Label Phase II Study in Patients Treated after Prior Chemotherapy That Contained Cisplatin or Carboplatin and Paclitaxel
    J Clin Oncol 16: 3345-332, 1998
       
    Paclitaxel and platinum have become a standard of care for advanced ovarian cancer. This makes second line or salvage therapy difficult, following a recurrence of ovarian cancer. This study of 139 patients with recurrent ovarian cancer and had earlier received paclitaxel and platinum received topotecan as second line.
      
    The overall response rate was 13.7% and only 12.4% for platinum resistant patients. It was associated with grade IV neutropenia in 82% of courses. The editor comments in view of such modest activity in recurrent ovarian cancer, topotecan may be considered in previously untreated patients along with other potent chemotherapy agents used in ovarian cancer.
         

  • Gore M, for the London Gynaecological Oncology Group [Royal Marsden Natl Health Service Trust, London]
    Randomized Trial of Dose-Intensity with Single-Agent Carboplatin in Patients With Epithelial Ovarian Cancer
    J Clin Oncol 16: 2426-2434, 1998
       
    Platinum drug are considered essential as first line chemotherapeutic agents in epithelial ovarian cancer & whether dose escalation of these drug would increase the survival. This study of 227 patients were assigned to AUC of 6 or 12 for 6 courses or 4 courses respectively. The progression free and overall survival did not differ between the two treatment groups although significant hematologic toxicity was observed in higher dosage arm. The editor comments that by increasing the dose of platinum 5-6 times the standard dose would require peripheral stem cell transfusion and whether this would be advantageous will require further randomized study for patients with advanced ovarian cancer.
        

  • Tai Y-T Lee S, Niloff E, et al [Dana-Farber Cancer Inst, Boston; Hrvard Med School, Boston]
    BAX Protein Expression and Clinical Outcome in Epithelial Ovarian Cancer
    J Clin Oncol 16: 2583-2590, 1998
      
    In vitro studies have shown that pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro.
       
    Forty five newly diagnosed patients with ovarian cancer were analyzed for BAX expression. The tumor tissue with high BAX expression had an improved clinical outcomes suggestive of an intact apoptotic pathway leading to chemo responsiveness of ovarian cancer to paclitaxel.
       

  • Markman M, Brady MF, Spirtos NM, et al [Cleveland Clinic Found, Ohio; Roswell Park Cancer Inst, Buffalo NY: Women’s Cancer Ctr of Northern California , Palo Alto; et al]
    Phase II Trial of Intraperitoneal Paclitaxel in Carcinoma of the Ovary, Tube and Peritoneum: A Gynecologic Oncology Group Study
    J Clin Oncol 16: 2620-2624, 1998
      
    This study of 76 patients with recurrent ovarian and fallopian tube cancer or primary carcinoma of the peritoneum were evaluated. The largest residual disease was 0.5 cm or less in maximum diameter. These patients received intra peritoneal paclitaxel.
     
    61% of the patients achieved complete response in patients with microscopic disease in contrast the response rate was only 3% with macroscopic disease moderate abdominal pain and neutropenia were the frequent side effects.
        

  • Brader KR, Morris M, Levenback C, et al [ Univ of Texas, Houston]
    Chemotherapy for Cervical Carcinoma : Factors Determining Response and Implications for Clinical Trial Design
    J Clin Oncol 16: 1879-1884, 1998
       
    The prognostic factors of the patients with cervical squamous cancer for response to palliative chemotherapy were studied in 190 chemonative patients. Older patients were more likely to respond and in patients in whom the recurrence is outside the irradiated field have a favourable response rate 25.2% compared to 5.3% for those with recurrence in the irradiated field. The editor comments that poor response to chemotherapy in such patients could be the poor vasculature due to previous surgery or radiation.
          

  • Cheng W-F, Chen C-A, Lee C-N, et al [Natl Taiwan Univ Hosp, Taipei]
    Vascular Endothelial Growth Factor in Cervical Carcinoma
    Obstet Gynecol 93: 761-765, 1999
      
    The expression of vascular endothelial growth factor [VEGF] is an angiogenesis stimulating cyto kene which is a forerunner of growth and metastasis in solid tumor.
      
    This study of 104 consecutive women with cervical cancer, VEGF levels were determined in cervical tissue specimen with clinical stage IB through IIA and from 30 consecutive women with benign disease. High VEGF levels were found in tumours larger than 4 cm and deep stromal invasion, lymphovascular emboli parametrial invasion or pelvic lymph node meastasis VEGF correlated with tumor size.
           

  • Obermair A, Tempfer C, Wasicky R, et al [Univ Hosp of Vienna]
    Prognostic Significance of Tumor Angiogenesis in Endometrial Cancer
    Obstet Gynecol 93: 367-371, 1999
      
    In this study of endometrial cancer specimens were stained with CD34 antigen and microvessels counted. Overall survival and microvessal density were compared. After adjusting for disease stage and histologic grade, microvessel density was an independent predictor of survival. The growth and spread of endometrial cancer depends on angiogenesis.
         

  • Alvarez AA, Krigman HR, Whitaker RS, et al [Duke Univ, Durham, NC]
    The Prognostic Significance of Angiogenesis in Epithelial Ovarian Carcinoma
    Clin Cancer Res 5: 587-591, 1999
      
    This study of 88 patients with ovarian cancer underwent staining, tissue section with antihuman endothelial cell antibodies to von Willebrand factor and CD31, tp determine the degree of angiogenesis. 
         
    The estimated median survival was 79 years for women with a microvessel density count of more than 10 or less and 2.7 years for women with less than 10. The degree of neovascularization was significantly and negatively related to the rate of survival 
    after adjusting for stage. Patients with low angiogenic counts have a significantly improved rate of survival.
         

  • Menon U, Talaat A, Jeyarajah AR, et al [St Bartholomew’s and Royal London School of Medicine and Dentistry; Harvard Med School, Boston]
    Ultrasound Assessment of Ovarian Cancer Risk in Postmenopausal Women With CA125 Elevation
    Br J Cancer 80: 1644-1647, 1999
         
    This study of 22,000 postmenopausal women, 45 years or older screened for CA125. Women with CA 125 levels 30 U/ml or higher underwent ultrasound [US]. Those with normal architecture on US had cumulative risk of ovarian cancer to be 0.15% similar to general population. Whereas those with abnormal ovarian architecture had cumulation risk of 24%. This group merits aggressive evaluation for ovarian cancer.
         

  • Du Bois A, Luck HJ, Bauknecht T, et al [Frauenklinik St Vincentius Hrankenhaus, Karlsruhe, Germany; Frauenklinik Medizinische Hochschule,Hannover, Germany; Universitatsfrauenklinik, Freiburg, Germany; et al]
    First-line Chemotherapy with Epirubicin, Paclitaxel, and Carboplatin for Advanced Ovarian Cancer : A Phase I/II Study of the Arbeitsgemeinschaft Gynakologische Okologie Ovarian Cancer Study Group
    J Clin Oncol 17: 46-51, 1999
     
    This study is to evaluate the maximum tolerated dose, safety, and feasibility of a 3-drug combination containing epirubicin with carboplatin and paclitaxel in previously untreated ovarian cancer.
      
    The maximum tolerated dose of epirubicin 60mg/m2 followed by paclitaxel 175 mg/m2 and carboplatin AUC5. Four of the seven achieved a complete remission 1 had partial response and 1 had progression and 10 of the fourteen with nonmeasurable disease had no evidence of disease after completion of treatment. This 3 drug combination had sufficient activity to warrant prospective randomized trials comparing paclitaxel carboplatin in previously untreated patients.
         

  • Hammond LA, Eckardt JR, Ganapathi R, et al [ Cancer Therapy and Research Ctr, San Antonio, Tex; Univ of Tex Health Science Ctr, San Antonio; Audie Murphy VA Hosp, San Antonio, Tex; et al]
    A Phase I and Translational Study of Sequential Administration of the Topoisomerase I and II Inhibitors Topotecan and Etoposide
    Clin Cancer Res 4: 1459-1467, 1998
        
    The main effect of topoisomerase I, topotecan [TPT] followed by topo II inhibitor such etoposide was assessed in patients with solid malignancies. As the main effect of topo1 and topo II inhibitors are two major classes of enzymes involved in regulating DNA topology in the cell. Although some clinical activity was observed. There was substantial toxicity and hence sequential treatment with these 2 agents would not be superior to either agents alone.
         

  • Parslov Michael, Lidegaard Ojvind, Klintorp Soren, et al, Copenhagen, Denmark
    Risk factors among young women with endometrial cancer: A Danish case-control study.
    Am J Obstet Gynecol 2000; 182: 23-29
      
    This study was undertaken to identify and quantify risk factors for endometrial cancer among young women.
      
    Endometrial cancer is a rare disease among premenopausal women. Seven percent of endometrial cancer occurs in women <50 years old. In the same age group about 300 curettage procedures and an equal number of endometrial biopsies are performed for every single diagnosis of endometrial cancer. When the physical complications attendant with these invasive procedures and the socioeconomic consequences of curettage as a screening procedure are considered, the question arises as to whether it is appropriate to carry out this number of intrauterine procedures in fertile women to find so few cases of endometrial malignancy.
       
    Several studies have identified risk factors of endometrial cancer among older women, such as overweight status, estrogen replacement therapy, nulliparity, infertility, diabetes mellitus, and hypertension. However, these risk factors are not necessarily relevant for endometrial cancer among young women.
      
    Hence this study was undertaken and findings were controlling for confounding influence from the other determinants revealed the following variables to be independent risk factors: family history of endometrial cancer, parity, age at first birth, number of induced abortions, use of oral contraceptives, and use of hormone replacement therapy.
      
    Women with a family history of endometrial cancer (mother or sister) had an odd ratio of endometrial cancer of 2.1 (95% confidence interval).
       
    Family predisposition: Family history of endometrial cancer in a first-degree relative (mother or sister) is a well-documented risk factor for endometrial cancer among both premenopausal and postmenopausal women, with odds ratios between 1.5 and 2.8. This relationship was confirmed by our data. It should be noted that the estimated odds ratio of 2.1 represents the impact of family predisposition after body mass index is controlled for. Thus the increased risk was caused by genetic circumstances other than adiposity.
      
    Diabetes and hypertension: In this study no significant association emerged between endometrial cancer and diabetes. Hypertension was not an independent risk factor.
        
    Cigarette smoking : In this study authors were not able to demonstrate an independent effect of smoking and anti-estrogenic effect of smoking.
      
    All studies have demonstrated a protective effect of cigarette smoking on the risk of development of endometrial cancer among postmenopausal women. It is remarkable that the protective influence of cigarette smoking has not been apparent in several studies on premenopausal women with endometrial cancer.
      
    Education : After adjustment for all variables, authors could not retrieve an association with years of schooling, which is a reliable indicator of social class.
      
    Etiologic fraction : With a mother or sister who had endometrial cancer the risk of development of endometrial cancer was increased by a factor of 2. Hormone replacement therapy increased risk by a factor of 3 but only about 2% of premenopausal women receive hormone replacement therapy. Consequently, the etiologic fraction of hormone replacement therapy was 4%. Oral contraceptive use of >1year; ³ 2 term pregnancies, age ³ 30 years when giving birth at first time, and a history of incomplete pregnancies are all conditions that decreased the risk of development of endometrial cancer.
        
    In conclusion, a number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women. These are family history of endometrial cancer, reproductive history, hormone replacement therapy, and the use of oral contraceptives.
      
    Increasing number of births reduced the risk of endometrial cancer. If all women gave birth ³ 2 times, about 40% of endometrial cancer in the premenopausal age group could be eliminated.
         

  • Gordon AN, Fleagle TJ, Guthrie D, et al 
    Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin (PLD) Versus Topotecan (TN)
    J Clin Oncol 2001, 19: 3312-3322 
    Literature Alert – Current Oncology Reports Vol. 3(6) November 2001 Pg. 456
           
    This phase
    III randomized multicenter study of 474 patients of ovarian carcinoma who had recurrence. These were stratified for platinum sensitive or refractory disease and for presence or absence of bulky disease.
          
    The patients were randomized to PLD or TN. In the overall analysis, the overall survival, progression free survival and response rates were similar. However, subgroup analysis PLD was superior to TN for both PFS and overall survival in patients with platinum sensitive relapse.
           
    In platinum resistant patients TN had a non statistically significant trend toward improved survival. No differences were seen for patients with or without bulky recurrent disease.
         

 

 

 

By |2022-07-20T16:42:23+00:00July 20, 2022|Uncategorized|Comments Off on Gynecologic Malignancies

About the Author: