A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer Journal Article
| Authors: | Leiser, A. L.; Maluf, F. C.; Chi, D. S.; Sabbatini, P.; Hensley, M. L.; Schwartz, L.; Venkatraman, E.; Spriggs, D.; Aghajanian, C. |
| Article Title: | A phase I study evaluating the safety and pharmacokinetics of weekly paclitaxel and carboplatin in relapsed ovarian cancer |
| Abstract: | This phase I study sought to determine the toxicity profile, pharmacokinetics, and antitumor activity of giving carboplatin every 3 weeks and paclitaxel weekly in patients with relapsed ovarian cancer. Eligible patients with relapsed epithelial ovarian cancer and prior treatment with platinum- and paclitaxel-based therapy were treated with an escalating regimen of carboplatin (day 1) at an area under the curve (AUC) of 4-6 and 1-h infusions of paclitaxel (days 1, 8, and 15) at 50-80 mg/m2 cycled at 3-week intervals. Pharmacokinetic studies were performed on the first day of cycles 1 and 2. All patients had a platinum-free interval of greater than 6 months from the most recent platinum treatment. A total of 77 cycles were administered to 16 patients, with a similar median number of cycles per patient at each dose level varying from 4.6 to 5.3. Febrile neutropenia and grade 4 thrombocytopenia were the dose-limiting toxicities at dose levels 3 and 4 after the third cycle, with no mucositis, nausea, vomiting, or peripheral neuropathy observed greater than grade 2. The maximum tolerated dose of carboplatin was an AUC of 5 and 80 mg/m2 for paclitaxel. Pharmacokinetic analysis showed a marginal statistical difference with regard to reduced systemic paclitaxel concentration after cycle 2 compared with cycle 1 (P = 0.06). Of nine patients evaluable for a radiographic response, the response rate was 66.6% with a complete response of 33.3%. All five patients with nonmeasurable disease achieved a biochemical response. The combination of carboplatin given every 3 weeks at an AUC of 5 and 1-h weekly paclitaxel at 80 mg/m2 is a feasible and reasonably well-tolerated regimen and may have significant antitumor activity in relapsed ovarian cancer patients. © 2007, IGCS and ESGO. |
| Keywords: | adult; clinical article; treatment outcome; aged; middle aged; antibiotic agent; clinical trial; drug tolerability; fatigue; neutropenia; area under the curve; diarrhea; drug safety; paclitaxel; cancer patient; ovarian cancer; ovarian neoplasms; carboplatin; multiple cycle treatment; nephrotoxicity; neoplasm recurrence, local; anemia; mucosa inflammation; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; peripheral neuropathy; drug administration schedule; steroid; antineoplastic activity; dose-response relationship, drug; arthralgia; drug dose escalation; drug hypersensitivity; febrile neutropenia; chemotherapy induced emesis; carcinoma; ovary carcinoma; cancer relapse; platinum derivative; maximum tolerated dose; phase 1 clinical trial; drug dose regimen; alopecia; antihistaminic agent; weekly; hematologic diseases; relapsed; cholinergic receptor blocking agent; platelet transfusion |
| Journal Title: | International Journal of Gynecological Cancer |
| Volume: | 17 |
| Issue: | 2 |
| ISSN: | 1048-891X |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2007-03-01 |
| Start Page: | 379 |
| End Page: | 386 |
| Language: | English |
| DOI: | 10.1111/j.1525-1438.2007.00811.x |
| PUBMED: | 17362316 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: IJGCE" - "Source: Scopus" |
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