Investigational new drugs
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Investigational new drugs · Feb 2014
Phase II trial of combination nab-paclitaxel, carboplatin and gemcitabine in first line therapy of advanced urothelial carcinoma.
Paclitaxel has significant single agent activity in urothelial cancer. The 130 nm albumin bound paclitaxel (nab-paclitaxel, ABI-007) delivers more paclitaxel to tumor than conventional paclitaxel without cremophor related toxicities. We assessed the efficacy of nab-paclitaxel in combination with carboplatin and gemcitabine as first line therapy in advanced urothelial cancer. ⋯ The combination of nab-paclitaxel, carboplatin and gemcitabine was poorly tolerated in this high risk patient population at these doses and schedule. Other nab-paclitaxel based combinations should be explored in first line therapy of advanced urothelial cancer.
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Investigational new drugs · Feb 2014
Feasibility of adding everolimus to carboplatin and paclitaxel, with or without bevacizumab, for treatment-naive, advanced non-small cell lung cancer.
One standard of care for advanced non-small cell lung cancer (NSCLC) is paclitaxel plus carboplatin ± bevacizumab. This two-step phase I study evaluated the feasibility of adding everolimus to paclitaxel plus carboplatin ± bevacizumab for advanced NSCLC. ⋯ The feasible everolimus doses given with carboplatin and paclitaxel ± bevacizumab were 5 mg/day and 30 mg/week. Neither schedule was very well tolerated in this unselected NSCLC population.
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Investigational new drugs · Oct 2013
Randomized Controlled Trial Multicenter Study Comparative StudyA randomized, multi-center, open-label, phase II study of once-per-cycle DA-3031, a biosimilar pegylated G-CSF, compared with daily filgrastim in patients receiving TAC chemotherapy for early-stage breast cancer.
A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. ⋯ Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.
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Investigational new drugs · Oct 2013
Multicenter StudyPhase I clinical and pharmacokinetic study of trabectedin and cisplatin given every three weeks in patients with advanced solid tumors.
The aim of this phase I study was to identify a feasible dose and schedule for the combination of cisplatin and trabectedin. The regimen evaluated consisted of cisplatin at a fixed dose of 75 mg/m(2) 1-hour intravenous (i.v.) infusion followed by escalating doses of trabectedin 3-hour i.v. infusion, both administered on day 1 every 3 weeks (q3wks). Two dose-limiting toxicities (DLTs), grade 4 neutropenia longer than 7 days duration and grade 3 vomiting despite standard antiemetic therapy, occurred at the starting dose of trabectedin (0.75 mg/m(2)). ⋯ Two partial responses were reported at the RD in patients with pretreated ovarian cancer. Comparison with population pharmacokinetic data suggests a PK interaction between trabectedin and cisplatin leading to increased plasma exposure of trabectedin in the first 48 h, lower platinum clearance and longer half-life. In conclusion, although the trabectedin dose achieved with this combination was low (50 % of single-agent when given q3wks), this day 1 q3wks trabectedin plus cisplatin combination showed a feasible administration, a tolerable safety profile and some antitumor activity.
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Investigational new drugs · Oct 2013
Efficacy, safety, and pharmacokinetics of imatinib dose escalation to 800 mg/day in patients with advanced gastrointestinal stromal tumors.
Imatinib dose escalation has been suggested as an effective therapy for advanced gastrointestinal stromal tumors (GIST) after progression on the standard dose. We evaluated the efficacy, tolerability, and pharmacokinetics of imatinib dose escalation. Eighty-four patients with GIST who received imatinib 800 mg/day as second-line therapy were reviewed. ⋯ The upper three quartiles of percent Cmin change associated with more frequent severe toxicities (56 %) than the lowest quartile (10 %; p=0.01). Dose escalation to 800 mg/day was active and feasible in GIST after progression on the standard dose. Imatinib Cmin monitoring may help to manage the patients with standard dose-resistant GIST that may require dose escalation.