A dose-escalating study of weekly bolus topotecan in previously treated ovarian cancer patients.

OBJECTIVE: Topotecan is an established topoisomerase I inhibitor for the treatment of relapsed ovarian cancer. Myelotoxicity and suboptimal patient convenience associated with daily topotecan, however, have prompted investigators to explore alternate regimens, including a weekly regimen of topotecan. The objective of this study was to determine the maximum tolerated dose (MTD) of topotecan given as a weekly bolus in previously treated ovarian cancer patients. METHODS: Second- and third-line ovarian cancer patients with measurable disease or elevated cancer antigen 125 received weekly bolus topotecan intravenously starting at 1.5 mg/m(2). Topotecan was escalated in dose increments of 0.5 mg/m(2) every 21 days as tolerability allowed. Dose-limiting toxicity was defined as grade 3/4 neutropenia or thrombocytopenia. RESULTS: Thirty-two of 35 patients were evaluable for safety and tolerability. No notable toxicity was observed with weekly topotecan doses < 4 mg/m(2). Additionally, there was an absence of dose-limiting myelotoxicity and thrombocytopenia with weekly topotecan. The MTD of weekly topotecan without the use of granulocyte colony-stimulating factor support was 4 mg/m(2), with grade 2 anemia, chronic fatigue, and grade 2 gastrointestinal toxicity limiting further dose escalation. Weekly topotecan also demonstrated antitumor activity at doses >2 mg/m(2). CONCLUSIONS: The establishment of a well-tolerated, weekly regimen of topotecan (4 mg/m(2), with a maximum recommended dose of 6 mg/m(2)) provides the basis for further investigation in phase II studies of single-agent and combination regimens in previously treated ovarian cancer patients.

Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.

BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report.

It is estimated that in 1988 there will be 12,900 cancers of the uterine cervix, representing 2.6% of cancers in women. Radiation therapy has been the primary mode of therapy/palliation; for the past 15-20 years survival results achieved with radiotherapy have plateaued. Attempts have been made to find agents to use with radiation aimed at decreasing recurrence and increasing survival. Phase II studies suggest cisplatin may be an excellent agent to combine with radiotherapy. This study was performed to evaluate the toxicity of this combination. Between December 10, 1980, and August 29, 1986, nine patients with advanced cervical cancer and poor prognosis and one patient with recurrent disease were enrolled. The Gynecologic Oncology Group (GOG) criteria for adverse effects were used in this study. Hematologic, gastrointestinal, genitourinary, and skin parameters were examined. Most adverse criteria had a score of 2 or less. Grade 2 nausea/vomiting was the most frequent problem. Anemia was the next most frequent and was the most serious problem encountered. Overall, the toxicity was acceptable; therefore it seems appropriate to proceed to larger studies to evaluate efficacy.

Malignant mixed mesodermal tumors of the ovary. A report of 13 cases.

The surgical pathology files at Thomas Jefferson University Hospital (TJUH) were reviewed for the period 1973-1984. Thirteen cases of primary ovarian malignant mixed mesodermal tumor (MMT) were found; however, material from only seven of these cases could be obtained for repeat review. No conclusions can be drawn regarding any impact on survival based on the histology. Treatment was highly varied reflecting the mix of physicians rendering treatment and the range of modalities used. Overall, survival was miserable. Six of the 13 patients (46.2%) survived 6 months or less, 10 of the 13 (76.9%) survived 12 months or less. No particular treatment modality seemed to offer enhanced survival unless aggressive cytoreductive surgery was performed. A plea is made for national cooperative groups to develop treatment protocols for this aggressive ovarian cancer.