Dataset Information

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study.

ABSTRACT:

Background

Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols.

Methods

Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate.

Results

Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1-6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively.

Conclusion

This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.

SUBMITTER: Nishimura M

PROVIDER: S-EPMC8286943 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study.

Nishimura Meiko M Sakai Hideki H Onoe Takuma T Boku Shogen S Yokoyama Takaaki T Kadokura Genmu G Morita Satoshi S Katsumata Noriyuki N Matsumoto Koji K

International journal of clinical oncology 20210526 8

<h4>Background</h4>Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols.<h4>Methods</h4>Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions o ...[more]

PMID: 34037884

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Project description:Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in patients with ovarian cancer. Secondary objectives were to describe safety and pharmacokinetics. Methods In this single-center trial the RP2D of metformin in combination with carboplatin area under the concentration-time curve (AUC) 6 and paclitaxel 175 mg/m2 every 3 weeks (q3w) in patients with advanced epithelial ovarian cancer was determined using a 3 + 3 escalation rule at three fixed dose levels: 500 mg three times daily (tds), 850 mg tds and 1000 mg tds. Metformin was commenced on day 3 of cycle 1 and continued until 3 weeks after the last chemotherapy administration. The RP2D was defined as the dose level at which 0 of 3 or ≤ 1 of 6 evaluable subjects experienced a metformin-related dose-limiting toxicity (DLT). Safety was assessed according to CTCAE v4.0. Plasma and serum samples for pharmacokinetic (PK) analyses were collected during treatment cycles 1 and 2. Results Fifteen patients with epithelial ovarian cancer and an indication for neo-adjuvant (n = 5) or palliative (n = 10) treatment were included. No DLTs were observed. Three patients discontinued study treatment during cycle 1 for other reasons than DLT. Six patients were treated at the RP2D of metformin 1000 mg tds. The most frequent low-grade toxicities were anemia, hypomagnesemia and diarrhea. Grade 3 adverse events (AEs) occurred in ten patients, most common were leucopenia (n = 4), thrombocytopenia (n = 3) and increased GGT (n = 3). There were no grade 4 AEs. Metformin increased the platinum (Pt) AUC (Δ22%, p = 0.013) and decreased the Pt clearance (Δ-28%, p = 0.013). Metformin plasma levels were all within the therapeutic range for diabetic patients (0.1-4 mg/L). Conclusion The RP2D of metformin in combination with carboplatin and paclitaxel in advanced ovarian cancer is 1000 mg tds. This is higher than the RP2D reported for combination with targeted agents. A potential PK interaction of metformin with carboplatin was identified.

Dataset Information

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study.

Background

Methods

Results

Conclusion

Publications

4-step, 2-h carboplatin desensitization in Japanese patients with ovarian cancer: a prospective study.

Similar Datasets

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