Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.

BACKGROUND: Ridaforolimus is a mammalian target of rapamycin inhibitor that has activity in solid tumors. Paclitaxel and carboplatin have broad antineoplastic activity in many cancers. This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers. METHODS: Eligible patients with advanced solid tumor cancers received oral 10 to 30 mg ridaforolimus daily for 5 consecutive days per week combined with intravenous paclitaxel (175 mg/m2) and carboplatin (area under the curve [AUC] 5-6 mg/mL/min) in 3-week cycles. A standard 3 + 3 design was used to escalate doses, with predefined changes to an alternate dosing schedule and/or changes in carboplatin AUC doses based on dose-limiting toxicity (DLT). Secondary information was collected regarding response and time to progression. Patients were continued on treatment if therapy was tolerated and if stable disease or better was demonstrated. RESULTS: Thirty-one patients were consented, 28 patients were screened, and 24 patients met eligibility requirements and received treatment. Two patients were replaced for events unrelated to drug-related toxicity, resulting in 22 DLT-evaluable patients. Two grade 4 DLTs due to neutropenia were observed at dose level 1. The next cohort was changed to a predefined alternate dosing schedule (days 1-5 and 8-12). DLTs were neutropenia, sepsis, mucositis, and thrombocytopenia. The most common adverse events were neutropenia, anemia, thrombocytopenia, fatigue, alopecia, nausea, pain, and leukopenia. Twenty-four patients received a median of 4 cycles (range, 1-12). Evaluable patients for response (n = 18) demonstrated a median tumor measurement decrease of 25%. The best response in these 18 patients included 9 patients with partial response (50%), 6 with stable disease (33%), and 3 with progressive disease (17%). Thirteen of these patients received treatment for 4 or more cycles. CONCLUSIONS: Treatment with ridaforolimus combined with paclitaxel and carboplatin had no unanticipated toxicities and showed antineoplastic activity. The recommended phase II dose and schedule is ridaforolimus 30 mg (days 1-5 and 8-12) plus day 1 paclitaxel (175 mg/m2) and carboplatin (AUC 5 mg/mL/min) on a 21-day cycle. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01256268 (trial registration date: December 1, 2010).

Comparison of Therapeutic G-CSF Cycles and Prophylactic G-CSF Cycles in Patients Receiving Paclitaxel and Carboplatin Combination Chemotherapy for Ovarian Cancer: A Retrospective Study Report.

OBJECTIVE: The aim of the present study was to investigate the differences between therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylactic G-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer. MATERIAL AND METHOD: Medical records of 15 women who received paclitaxel and carboplatin combination chemotherapy for ovarian cancer between January 2003 and December 2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel and carboplatin as the first-line chemotherapy. The complications were compared between therapeutic G-CSF cycles and prophylactic G-CSF cycles. RESULTS: The number of chemotherapy cycles correlated with the ratio of prophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injections were chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophil counts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSF cycles. However, there were no significant differences in the intervals of chemotherapy, delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSF and prophylactic G-CSF cycles. CONCLUSION: Prophylactic G-CSF injections were not effective in preventing the incidence of febrile neutropenia in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.

Comparison of Therapeutic G-CSF Cycles and Prophylactic G-CSF Cycles in Patients Receiving Paclitaxel and Carboplatin Combination Chemotherapy for Ovarian Cancer: A Retrospective Study Report / Journal of Rural Medicine

<b>Objective:</b> The aim of the present study was to investigate the differencesbetween therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylacticG-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy forovarian cancer.<br><b>Material and Method:</b> Medical records of 15 women who received paclitaxel andcarboplatin combination chemotherapy for ovarian cancer between January 2003 and December2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel andcarboplatin as the first-line chemotherapy. The complications were compared betweentherapeutic G-CSF cycles and prophylactic G-CSF cycles.<br><b>Results:</b> The number of chemotherapy cycles correlated with the ratio ofprophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injectionswere chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophilcounts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSFcycles. However, there were no significant differences in the intervals of chemotherapy,delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSFand prophylactic G-CSF cycles.<br><b>Conclusion:</b> Prophylactic G-CSF injections were not effective in preventingthe incidence of febrile neutropenia in patients receiving paclitaxel and carboplatincombination chemotherapy for ovarian cancer.

Comparison of therapeutic G-CSF cycles and prophylactic G-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer: A retrospective study report / Journal of Rural Medicine

<b>Objective:</b> The aim of the present study was to investigate the differences between therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylactic G-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.<br><b>Material and Method:</b> Medical records of 15 women who received paclitaxel and carboplatin combination chemotherapy for ovarian cancer between January 2003 and December 2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel and carboplatin as the first-line chemotherapy. The complications were compared between therapeutic G-CSF cycles and prophylactic G-CSF cycles.<br><b>Results:</b> The number of chemotherapy cycles correlated with the ratio of prophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injections were chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophil counts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSF cycles. However, there were no significant differences in the intervals of chemotherapy, delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSF and prophylactic G-CSF cycles.<br><b>Conclusion:</b> Prophylactic G-CSF injections were not effective in preventing the incidence of febrile neutropenia in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.