Treatment Tolerance and Side Effects of Intraperitoneal Carboplatin and Dose-Dense Intravenous Paclitaxel in Ovarian Cancer.

OBJECTIVE: To describe the frequency of clinically significant side effects associated with adjuvant intraperitoneal (IP) carboplatin and intravenous (IV) dose-dense paclitaxel chemotherapy for epithelial ovarian cancer (EOC). METHODS: Patients with stage II to IV EOC who underwent upfront cytoreductive surgery followed by adjuvant IP carboplatin (AUC 6) every 3 weeks with IV paclitaxel weekly at 80 mg/m2 were included. Side effects and the resulting changes in treatment are presented using univariate analysis and compared to major phase III RCTs. RESULTS: Between March 2013 and October 2015, 49 patients comprising 289 cycles of chemotherapy were included in the analysis; 43 patients (87.8%) completed six cycles of chemotherapy and 38 (77.6%) completed six cycles of IP carboplatin. Treatment was discontinued early due to neuropathy (5/49) and disease progression (1/49). Carboplatin IV was substituted due to port access (3/49) and poor postoperative performance status (3/49). Neutropenia occurred in 16 patients (32.7%). Fourteen patients (28.6%) required red blood cell transfusion. Thrombocytopenia affected nine patients (18.4%). Infection delaying treatment occurred in five patients (10.4%). Gastrointestinal and renal toxicity occurred in four (8.1%) and one patient (2.0%), respectively. Four patients experienced a taxane reaction. No patients experienced ototoxicity, fistula formation, chemotherapy leakage, or severe abdominal pain. CONCLUSION: Carboplatin IP and weekly IV paclitaxel was well-tolerated with a side-effect profile similar to or better than previously published traditional treatment regimens.

Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach.

PURPOSE: To determine the feasibility of adjuvant paclitaxel and carboplatin chemotherapy interposed with involved field radiotherapy for women with advanced endometrial cancer. METHODS AND MATERIALS: This was a prospective cohort study of women with Stage III and IV endometrial cancer. Adjuvant therapy consisted of 4 cycles of paclitaxel (175 mg/m(2)) and carboplatin (350 mg/m(2)) every 3 weeks, followed sequentially by external beam radiotherapy (RT) to the pelvis (45 Gy), followed by an additional two cycles of chemotherapy. Para-aortic RT and/or HDR vault brachytherapy (BT) were added at the discretion of the treating physician. RESULTS: Thirty-three patients (median age, 63 years) received treatment between April 2002 and June 2005. Median follow-up was 21 months. Stage distribution was as follows: IIIA (21%), IIIC (70%), IVB (9%). Combination chemotherapy was successfully administered to 30 patients (91%) and 25 patients (76%), before and after RT respectively. Nine patients (27%) experienced acute Grade 3 or 4 chemotherapy toxicities. All patients completed pelvic RT; 19 (58%) received standard 4-field RT and 14 (42%) received intensity-modulated radiotherapy. Ten (30%) received extended field radiation. Four patients (12%) experienced acute Grade 3 or 4 RT toxicities. Six (18%) patients developed chronic RT toxicity. There were no treatment-related deaths. Two-year disease-free and overall survival rates were both 55%. There was only one pelvic relapse (3%). CONCLUSIONS: Adjuvant treatment with combination chemotherapy interposed with involved field radiation in advanced endometrial cancer was well tolerated. This protocol may be suitable for further evaluation in a clinical trial.

Systematic review of systemic therapy for advanced or recurrent endometrial cancer.

OBJECTIVE: To evaluate the chemotherapeutic options for women with advanced or recurrent endometrial cancer. METHODS: The MEDLINE, CANCERLIT and the Cochrane Library databases were searched from 1984 to March 2005 for randomized controlled trials (RCTs) comparing chemotherapy regimens in patients with advanced or recurrent endometrial cancer. Studies were included only if patients had measurable or evaluable disease, and/or response rates were reported. RESULTS: Seventeen RCTs compared regimens involving chemotherapy and/or hormonal therapies. Three chemotherapy trials demonstrated a statistically significant difference in response rates between treatment arms, but only one of these trials showed a modest survival advantage. The addition of cisplatin to doxorubicin in two RCTs significantly improved response rates (1.7- to 2.5-fold higher) but did not impact on survival. In two other RCTs using cisplatin and doxorubicin as standard therapy, the addition of paclitaxel improved response rates (57% versus 34%) and median survival (15.3 versus 12.3 months) when combined with cisplatin and doxorubicin but not when combined with doxorubicin only. Toxicity was increased with the three-drug combination. Quality of life was assessed in one trial, which is currently only in abstract form. Medroxyprogesterone acetate (200 mg/day) was effective in one RCT, particularly in patients with well-differentiated, receptor-positive tumors. CONCLUSIONS: Combination chemotherapy with doxorubicin and cisplatin results in higher response rates than doxorubicin alone. The addition of paclitaxel to either of these regimens resulted in a small survival advantage in one trial using all three drugs. In light of the limited survival advantage associated with this regimen, the use of less toxic combinations of taxanes with carboplatin requires further study. Medroxyprogesterone acetate is useful in selected patients.