Cisplatin as initial chemotherapy in ovarian carcinosarcomas: a Gynecologic Oncology Group study.
ABSTRACT Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data on cisplatin, the first of the agents to be studied in this disease.
One hundred thirty-six eligible patients with ovarian carcinosarcoma received cisplatin (50 mg/m(2)) every 3 weeks until disease progression or unacceptable toxicity.
Among 44 patients evaluable for response, one complete (2%) and eight partial (18%) responses resulted. An additional 10 (23%) patients exhibited stable disease, while 25 (57%) had increasing disease. Median progression-free survival in 130 patients evaluable for this endpoint was 5.2 months. Median survival in the same 130 patients was 11.7 months. Adverse effects >/=grade 2 among the 132 patients evaluable for toxicity included leukopenia (14%), neutropenia (17%), thrombocytopenia (2%), anemia (10%), nausea and vomiting (40%), azotemia (3%), neurotoxicity (4%), fever (2%), and tinnitus (1%).
These data provide the first objective evidence that cisplatin is active as an initial therapy for patients who have carcinosarcoma of the ovary. The overall response rate (20%) is similar to that seen in carcinosarcomas of the uterus.
Article: Ovarian carcinosarcomas: clinicopathological prognostic factors and evaluation of chemotherapy regimens containing platinum.[show abstract] [hide abstract]
ABSTRACT: To evaluate the clinicopathological prognostic factors and outcome of chemotherapy in ovarian carcinosarcomas. We reviewed the records of 26 patients treated from 1990 to 2006 at the Oncology Institute of Istanbul University. Clinical data including demographics, stage, surgery, chemotherapy, and survival were collected from patients' charts. All patients underwent initial debulking surgery. Optimal debulking was achieved in 21 (81%) patients. The most striking clinicopathological finding was the high incidence of hemorrhagic ascites (n: 6) which was observed in 60% of the patients with ascites (n: 10). The overall median survival of the patients was 26 months. Residual disease was associated with a decreased overall survival, P=0.04. Median survival (50 months vs 9.7 months, P=0.042) of the patients with early stage disease were longer than the patients with advanced stage. Twenty-two patients received platinum-based combination chemotherapy. There was a trend for increased median survival in the patients who were treated with carboplatin/paclitaxel combination (P=0.066). Although the numbers were insufficient for statistical evaluation, the patients treated with ifosfamide combinations had improved survival (36 months vs 26 months). However, when the patients treated with ifosfamide and carboplatin/paclitaxel combinations were combined, survival was statistically improved compared to the other regimens (36 months vs 9.7 months, P=0.04). Chemotherapy regimens containing doxorubicin or cyclophosphamide were not encouraging. Stage (P=0.02) and adjuvant platinum-based chemotherapy containing either paclitaxel or ifosfamide (P=0.024) remained predictive of outcome in the multivariate analysis. Hemorrhagic ascites can be used in the initial differential diagnosis of ovarian carcinosarcomas. Stage, optimal debulking and type of adjuvant therapy were statistically significant prognostic predictors of ovarian carcinosarcomas. We advise that patients with ovarian carcinosarcomas should be treated by optimal cytoreduction followed by adjuvant platinum/taxan or platinum/ifosfamide combinations.Gynecologic Oncology 02/2008; 108(1):136-40. · 3.89 Impact Factor
Article: Platinum, anthracycline, and alkylating agent-based chemotherapy for ovarian carcinosarcoma.[show abstract] [hide abstract]
ABSTRACT: Ovarian carcinosarcoma (OCS) is a rare malignancy associated with a poor prognosis. Platinum, anthracyclines, and alkylating agents are the most effective antiblastic drugs for treatment of gynecologic epithelial and stromal tumors. The aim of this study was to determine response rate and overall survival (OS) of patients with OCS who were treated with a combination of these 3 drugs. Forty-one women with OCS who were referred to the Department of Gynecologic Oncology of San Gerardo Hospital in Monza and European Institute of Oncology in Milan, between January 1995, and December 2006, and treated with a combination regimen of cisplatin, adriamycin, and cyclophosphamide or a combination regimen containing of cisplatin, epirubicin, and ifosfamide plus granulocyte colony-stimulating factor were considered for this study. Four women had OCS stage I; 7, stage II; 23, stage III; and 7, stage IV. Heterologous, homologous, and mixed stromal components were described in 17, 14, and 10 patients, respectively. Thirteen women were treated with a combination of cisplatin, adriamycin, and cyclophosphamide and 28 with a combination of cisplatin, epirubicin, and ifosfamide plus granulocyte colony-stimulating factor. Two women did not complete their treatment because of the rapid progression of their disease and severe toxicity. Among 22 women considered evaluable for response, 10 (46%) achieved a complete response and 3 (13%) achieved a partial response (global response rate, 59%). Overall progression-free survival was 11.8 months (range, 0.9-96 months) and 13.8 and 10.1 months in stage I-II and III-IV, respectively (P = 0.13). Median OS was 20 months (range, 1-123 months), not reached in stage I-II, and 19.7 months in stage III-IV (P = 0.07). No significant difference between homologous and heterologous sarcomatous components was observed (P = 0.95), whereas no significant trend of improved OS was noticed for stage IIIC-IV with optimal debulking surgery (n = 9), compared with suboptimal cytoreduction (n = 19; 32.6 vs 14.5 months, P = 0.14). The combination of anthracycline, alkylating agent, and cisplatin showed a good response rate but also a high toxicity. The prognosis of OCS remains poor. Optimal cytoreduction may improve survival, but new anticancer drugs or more effective regimens are awaited.International Journal of Gynecological Cancer 08/2009; 19(6):1142-6. · 1.65 Impact Factor
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ABSTRACT: Rare tumors, when considered as a group, represent a significant burden to society as they may account for up to 25% of the mortality by cancer in nations like the United States. In contrast with the current scenario in highly incident cancer types, little progress has been achieved in the treatment of the most rare cancers. The reasons for this apparent stagnation are mostly intrinsic to logistical difficulties in performing large clinical trials in rare diseases and will be addressed further in this article. Because both cancer incidence and clinical research are booming in emerging nations, we also aim to address the current and future role of these countries in research and the drug development process in rare tumor types.Rare tumors 01/2010; 2(3):e49.