The following articles appeared in this month's issues of the surveyed journals. Articles that seem to be of most interest to the practicing gynecologic oncologist are included. The journals that are surveyed are New England Journal of Medicine, Journal of Clinical Oncology, Gynecologic Oncology, Cancer, American Journal of Obstetrics and Gynecology, Lancet, Cancer Research, Obstetrics and Gynecology, Journal of the National Cancer Institute, Journal of the American Medical Association. The participants in this program are the active clinical fellows at Memorial Hospital: Bhavana Pothuri, Mario Leitao, Christopher Awtrey, Sarah Ferguson, Alan Schlaerth and Rami Eitan. The managing editor is Douglas Levine. Comments, questions, complaints and suggestions are always welcome, please E-mail us at: VJC@smgo.org or click here.  To subscribe or unsubscribe to the VJC, click here.

Gynecologic Oncology – Mario Leitao

Title: Gemcitabine Reverses Cisplatin Resistance: Demonstration of Activity in Platinum- and Multidrug-Resistant Ovarian and Peritoneal Carcinoma

Authors: Peter G. Rose, Kim Mossbruger, Nancy Fusco, Mary Smrekar, Sue Eaton and Michael Rodriguez

Source: Gynecologic Oncology, Volume 88, Issue 1, January 2003, Pages 17-21.

Summary: 36 patients with platinum- and paclitaxel- resistant ovarian cancer were given gemcitabine (750mg/m2)/cisplatin (30mg/m2) on Day 1 and 8 every 21 days. 35 were evaluable with 15 patients responding (42.9%; 11 PRs and 4 CRs). Median response duration was 11 months (range 4-14 months), progression-free interval was 6 months (1-14 months) and median survival was 12 months. Authors conclude that this is combination is active in platinum- resistant patients, but associated with some toxicity.

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Title: Weekly Low-Dose Carboplatin and Paclitaxel in the Treatment of Recurrent Ovarian and Peritoneal Cancer

Authors: Laura J. Havrilesky, Angeles A. Alvarez, Robyn A. Sayer, Johnathan M. Lancaster, John T. Soper, Andrew Berchuck, Daniel L. Clarke-Pearson, Gustavo C. Rodriguez and Michael E. Carney

Source: Gynecologic Oncology, Volume 88, Issue 1, January 2003, Pages 51-57.

Summary: 29 evaluable patients (21 platinum-sensitive and 8 platinum-resistant) were treated with carboplatin (AUC2) and paclitaxel (80mg/m2) on days 1, 8 and 15 of a 28 day cycle. The overall response rate (RR) was 83% (16 CRs and 8 PRs). For platinum-sensitive patients the RR was 100% (15 CRs and 6 PRs) and for platinum-resistant it was 38% (1 CR and 2 PRs). The median time to progression, time to response and duration of response for the entire group was 12 months, 9 weeks and 10 months, respectively. Anemia was seen in 50% of patients, neutropenia in 86% and thrombocytopenia in 32%.

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Journal of Clinical Oncology - Bhavana Pothuri

Title: Evaluation of Monoclonal Humanized Anti-HER2 Antibody, Trastuzumab, in Patients With Recurrent or Refractory Ovarian or Primary Peritoneal Carcinoma With Overexpression of HER2: A Phase II Trial of the Gynecologic Oncology Group

Authors: Bookman, Michael A., Darcy, Kathleen M., Clarke-Pearson, Daniel, Boothby, Richard A., Horowitz, Ira R.

Source: J Clin Oncol 2003 21: 283-290.

Summary: Of 837 tumor samples analyzed for HER2 expression, 95 (11%) exhibited expression. Of 45 patients with recurrent disease, 41 were eligible. A response rate of 7% was noted with mild expected toxicities, and no treatment related mortalities. There was no evidence of host anti-trastuzumab antibody formation. The value of single agent trastuzumab in recurrent ovarian cancer is limited due to low rate of HER2 over-expression and low rate of response.

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Title: Phase II Trial of Irinotecan in Patients With Metastatic Epithelial Ovarian Cancer or Peritoneal Cancer

Authors: Bodurka, Diane C., Levenback, Charles, Wolf, Judith K., Gano, Jacalyn, Wharton, J. Taylor, Kavanagh, John J., Gershenson, David M.

Source: J Clin Oncol 2003 21: 291-297.

Summary: 31 patients with measurable disease were enrolled: 25 were treated with Irinotecan 300 mg/m2 every 3 wks, while 6 were treated with 250 mg/m2 due to age>65 years. Overall response rate was 17.2 %, 1 CR (3%) and 4 PRs (14%), 14 (48%) with stable disease, and 10 with (35%) progression. Median PFS was 3mos, and median duration of response was 1mos. Median survival from initiation of irinotecan was 10mos. Major toxicities occurred though there were no tx related deaths noted. Irinotecan has substantial toxicity and moderate efficacy in patients with platinum refractory EOC or PPC.  

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Journal of the National Cancer Institute – Rami Eitan

Title: International Collaborative Ovarian Neoplasm Trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm Trial: Two Parallel Randomized Phase III Trials of Adjuvant Chemotherapy in Patients With Early-Stage Ovarian Carcinoma

Authors: ICON1 and EORTC–ACTION

Source: J Natl Cancer Inst 2003; 95: 105-112.

Summary: This is a combined analysis of 925 patients from the ICON 1 and EORTC-ACTION trials. Overall survival at 5 years was 82% in the chemotherapy arm and 74% in the observation arm (p=0.008). PFS was also found to be better in the chemotherapy arm. The authors conclude that adjuvant chemotherapy provides a benefit in overall and PFS in patients with early stage ovarian cancer, but they emphasize that only one sixth of the patients were optimally staged and that this group may not have benefited from chemotherapy as did the others.

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Title: Impact of Adjuvant Chemotherapy and Surgical Staging in Early-Stage Ovarian Carcinoma: European Organisation for Research and Treatment of Cancer–Adjuvant ChemoTherapy in Ovarian Neoplasm Trial

Authors: J. Baptist Trimbos, Ignace Vergote, Giorgio Bolis, Jan B. Vermorken, Constantino Mangioni, Caterina Madronal, Massimo Franchi, Saverio Tateo, Gerardo Zanetta, Giovanna Scarfone, Livia Giurgea, Petra Timmers, Corneel Coens, and Sergio Pecorelli

Source: J Natl Cancer Inst 2003; 95: 113-125.

Summary: The EORTC-ACTION trial randomized 448 patients with early ovarian cancer to platinum based chemotherapy or observation. One third of patients were optimally staged. There was no difference found in overall survival between the 2 treatment arms. PFS was better in the adjuvant arm. Among patients in the observation arm, optimal staging was associated with improvement in overall and PFS. No such association was found in the chemotherapy arm. In the non-optimally staged patients chemotherapy was associated with improved overall and PFS. The benefit of adjuvant chemotherapy appeared to be limited to patients who were not optimally staged – patients at more risk of unrecognized residual disease.

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Title: International Collaborative Ovarian Neoplasm Trial 1: A Randomized Trial of Adjuvant Chemotherapy in Women With Early-Stage Ovarian Cancer

Authors: ICON1

Source: J Natl Cancer Inst 2003; 95: 125-132.

Summary: The ICON 1 trial randomized 477 patients with early stage ovarian cancer to adjuvant or no adjuvant treatment. There is no data on the quality of the staging procedure performed. Patients in the adjuvant chemotherapy arm had better overall survival (P=0.03), and better PFS (P=0.01). The authors concluded that the results suggest that platinum based adjuvant chemotherapy improves survival and delays recurrence in patients with early stage disease.

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Obstetrics and Gynecology – Alan Schlaerth

Title: Screening interval and risk of invasive squamous cell cervical cancer

Authors: Marie Grisham Miller, Hai-Yen Sung, George F. Sawaya, Kathleen A. Kearney, Walter Kinney and Robert A. Hiatt

Source: Obstetrics & Gynecology, Volume 101, Issue 1, January 2003, Pages 29-37.

Summary: 482 patients with invasive squamous cell carcinoma of the cervix were matched with controls to compare the risk of developing carcinoma with screening intervals of 1,2, and 3 years after a negative cervical smear. The relative risks of developing squamous cell carcinoma of the cervix were significantly greater for 2-year and 3-year screening intervals compared with a one year interval (RR 1.72 for 2 year interval and RR 2.06 for 2 year interval compared to one year screening interval).

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Title: Cervical cancer: effect of glandular cell type on prognosis, treatment, and survival

Authors: Margaret L. J. Davy, Tom J. Dodd, Colin G. Luke and David M. Roder

Source: Obstetrics & Gynecology, Volume 101, Issue 1, January 2003, Pages 38-45.

Summary: To investigate the importance of glandular histology in cervical cancer on prognosis and survival data was collected from 1984-2000 comparing disease-specific survival, age at diagnosis, diagnostic period, stage, grade, and primary course of treatment. The authors report that the incidence of adenocarcinoma of the cervix is increasing and that adenocarcinoma has a higher case fatality than squamous cell lesions (RR= 2.08).

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Title: Venous thromboembolism prophylaxis: patients at high risk to fail intermittent pneumatic compression

Authors: Daniel L. Clarke-Pearson, Richard K. Dodge, Ingrid Synan, R. Craig McClelland and G. Larry Maxwell

Source: Obstetrics & Gynecology, Volume 101, Issue 1, January 2003, Pages 157-163.

Summary: 1862 consecutive gynecologic surgery patients who failed intermittent pneumatic compression were reviewed. Multivariable regression analysis found that diagnosis of cancer (P=.001), history of deep venous thrombosis (P=.006), and age greater than 60 (P=.04) were independent prognostic factors. Patients with two or three of these variables had a 3.2% incidence of developing thromboemboli. If patients had none or one risk factor, the incidence of thromboemboli dropped to 0.6%. These factors identify a high risk group that might be considered for more intense prophylaxis.

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American Journal of Obstetrics and Gynecology – Chris Awtrey

Title: Radical trachelectomy and pelvic lymphadenectomy with uterine preservation in the treatment of cervical cancer

Authors: John B. Schlaerth, Nicola M. Spirtos and Alan C. Schlaerth

Source: American Journal of Obstetrics and Gynecology, Volume 188, Issue 1, January 2003, Pages 29-34.

Summary: The experience with radical trachelectomy in 10 patients between 1995 and 1999 is described. 8 had stage IA2 disease and 2 had stage Ib. 6 of the 10 had adenocarcinoma. There were 2 intra-operative cystotomies and 1 pelvic hematoma. With a mean follow up of 47.6 months there have been no recurrences and 4 pregnancies. Two ended in mid-term losses and two pregnancies resulted in live births, at 32 and 38 weeks. The authors conclude that this is a reasonable form of treatment for a select group of patients with cervical cancer who wish to preserve fertility.

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New England Journal of Medicine – Bhavana Pothuri

Nothing of interest this month

Journal of the American Medical Association – Rami Eitan

Cancer – Sarah Ferguson

Title: Prognostic factors in neuroendocrine small cell cervical carcinoma.  A multivariate analysis

Authors: John K. Chan, Vera Loizzi, Robert A. Burger, Joanne Rutgers, Bradley J. Monk

Source: Cancer Volume 97, Issue 3, 2003. Pages: 568-574

Summary: To determine clinical and pathologic factors associated with survival in small cell carcinoma of the cervix 34 patients with NE cervical carcinoma were retrospectively studied. Women with early stage disease (stage I-IIA) had median survival of 31 months compared to 10 months in advanced stage disease (≥stage IIB) (p<0.002). On multivariate analysis, advanced stage and smoking were independent poor prognostic factors for survival.

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Lancet – Chris Awtrey

Nothing of interest this month

Cancer Research – Sarah Ferguson

Title: Microarray Analysis Reveals Distinct Gene Expression Profiles among Different Histologic Types of Endometrial Cancer

Authors: Risinger, John I., Maxwell, G. Larry, Chandramouli, G. V. R., Jazaeri, Amir, Aprelikova, Olga, Patterson, Tricia, Berchuck, Andrew, Barrett, J. Carl

Source: Cancer Res 2003 63: 6-11

Summary: To determine the molecular events in endometrial carcinogenesis. 13 serous, 3 clear cell, 19 endometrioid and 7 age matched normal endometrium were evaluated using a cDNA microarray with 9984 transcripts.  There were 191 genes with a greater than 2-fold difference in expression between the 3 histologic subgroups (p<0.001) by hierarchical clustering suggesting previously unrecognized novel pathways involved in the development of endometrial cancers.

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