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Platinum-based chemotherapy should not be delayed for relapsed ovarian cancer
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Platinum-based chemotherapy should not be delayed in favor of nonplatinum-based chemotherapy for the treatment of women with partially platinum-sensitive progressing ovarian cancer, according to a randomized controlled study published in Journal of Clinical Oncology.
Most patients treated for ovarian cancer experience progression after surgery and first-line platinum-based chemotherapy. Subsequent treatment with platinum-based chemotherapy among patients with progressing ovarian cancer may be more effective with a longer interval from previous platinum treatment.
“The time from last platinum treatment to recurrence drives a treatment strategy that is based on nonplatinum chemotherapy if platinum-free interval is less than 6 months, and on platinum-containing doublets if platinum-free interval is more than 12 months,” Sandro Pignata, MD, from the uro-gynecological department in the division of medical oncology of Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale” in Naples, Italy, and colleagues wrote. “There is uncertainty when the platinum-free interval is between 6 and 12 months because of unsatisfactory results from treatment with platinum-containing doublets.”
In 1999, researchers developed a hypothesis suggested the prolongation of platinum-free interval with a single-agent nonplatinum-based chemotherapy could improve outcomes by increasing sensitivity to platinum. However, a 2006 retrospective study conducted by the Multicenter Italian Trials in Ovarian Cancer (MIT) group suggested using a nonplatinum single agent was not the best choice.
In 2008, Pignata and colleagues launched the international, multicenter, randomized, open-label phase 3 MITO-8 trial to determine whether prolonged platinum-free interval through the introduction of nonplatinum treatment improved outcomes in women with partially platinum-sensitive recurrent ovarian cancer.
The researchers randomly assigned patients to receive standard therapy (n = 108) — platinum-based chemotherapy at current relapse followed by nonplatinum-based chemotherapy at subsequent relapse — or experimental therapy (n = 107) of nonplatinum-based chemotherapy at current relapse followed by platinum-based chemotherapy at subsequent relapse.
OS served as the primary endpoint. Secondary endpoints included PFS after the two planned treatments (PFS2), total response rate, total toxicity, PFS after the first planned treatment (PFS1) and quality of life.
Patients in the experimental arm demonstrated prolonged median platinum-free interval from random assignment (7.8 months vs. 0.01 months) and from the last platinum injection received before study entry (15.8 months vs. 8 months).
However, patients in the experimental arm did not demonstrate an OS benefit compared with patients in the standard arm (median OS, 21.8 months vs. 24.5 months; HR = 1.38; 95% CI, 0.99-1.94).
Researchers included 177 events in the PFS2 analysis. Results showed PFS appeared significantly shorter in the experimental arm (median PFS, 12.8 months vs. 16.4 months; HR = 1.41; 95% CI, 1.04-1.92).
After 202 events included in the PFS1 analysis, median PFS was 9 months (95% CI, 7.6-10.4) in the standard arm and 5 months (95% CI, 4.1-5.9) in the experimental arm.
Researchers had data evaluable for objective response from 131 patients according to RECIST criteria. Thirty-six patients (56%) in the standard arm and 29 patients (43%) in the experimental arm achieved an objective response.
Similarly, among 142 patients evaluable according to Gynecological Cancer Intergroup criteria, 49 patients (75%) in the standard arm and 54 patients (70%) in the experimental arm achieved an objective response.
Global health status and quality-of-life score after three cycles of treatment worsened significantly in the experimental arm (P = .003).
Only slight differences in adverse events occurred. More patients in the standard arm experienced any-grade neutropenia (69.5% vs. 55.1%), musculoskeletal symptoms (3.8% vs. 0%) and neuropathy (50.5% vs. 33.6%), as well as severe nausea (3.8% vs. 0%).
“MITO-8 strongly supports the recommendation that platinum re-challenge not be delayed in favor of a nonplatinum treatment [among] patients with partially platinum-sensitive ovarian cancer,” Pignata and colleagues wrote. “It is also advisable that platinum-based chemotherapy be used as the control arm in future trials of new drugs in this setting.” – by Kristie L. Kahl
Disclosures: Pignata reports honoraria from AstraZeneca, PharmaMar and Roche; consultant/advisory roles with AstraZeneca, Pfizer, PharmaMar, Roche and Tesaro; and research funding from Merck Sharp & Dohme, Pfizer and Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.
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