Apr 27, 2015
For women with metastatic or recurrent cervical cancer, paclitaxel plus carboplatin confers the same survival advantage as paclitaxel plus cisplatin, currently the standard of care (overall survival [OS] was 17.5 months in the carboplatin group versus 18.3 months in the cisplatin group). That’s according to the first phase III trial to compare the carboplatin-based combination with the cisplatin-based combination. However, while the study found that OS was the same between patients who received the two drugs, differences emerged when patients were separated out by their platinum history: Among patients who were receiving a platinum for the first time, cisplatin conferred a survival advantage (OS in the cisplatin group was 23 months versus 13 months in the carboplatin group). For patients who received one dose of platinum before enrolling on the trial, carboplatin conferred a survival advantage. The study, “Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Cisplatin in Metastatic or Recurrent Cervical Cancer: The Open-Label Randomized Phase III Trial JCOG0505,” was published in the Journal of Clinical Oncology (JCO), online, ahead of print, March 2.
First author Ryo Kitagawa, MD, said that in light of these findings, “Paclitaxel plus carboplatin should now be a standard treatment option for metastatic or recurrent cervical cancer. However, cisplatin is still the key drug for patients who have not received prior cisplatin-based treatment, such as those with primary stage IVB cervical cancer.”
The study enrolled 250 patients from multiple centers across Japan from 2006 to 2009
Benefits of carboplatin versus cisplatin: fewer hospitalizations and less neurotoxicity
The JCO article states that, historically, cisplatin has been considered the most active palliative chemotherapy for metastatic or recurrent cervical cancer. Paclitaxel added to cisplatin does not confer greater overall survival (OS), but it does deliver a greater response rate and longer median progression-free survival.
According to Dr. Kitagawa, carboplatin, whose effectiveness compared to cisplatin had never before been studied in a phase III trial, has several advantages.
“Carboplatin has been reported to be a less effective platinum analogue than cisplatin for cervical cancer, but it induces milder nephropathy, less nausea/vomiting, and lower neuropathy than cisplatin,” said Dr. Kitagawa. In addition, the combination of carboplatin and paclitaxel allows for outpatient treatment, as opposed to the combination of paclitaxel and cisplatin, which is administered over 24 hours, thus requiring hospitalization with each cycle.
In terms of toxicity, the current JCO study found that the patients in the cisplatin group reported significantly greater grade 4 neutropenia (75% of patients versus 45.2%); in addition, grade 3 to 4 febrile neutropenia, creatinine elevation, and nausea/vomiting tended to be higher in this group. Among the patients who received carboplatin, thrombocytopenia and sensory neuropathy tended to be higher, compared to patients in the cisplatin group.
Resistance to cisplatin might explain findings
One explanation for why carboplatin might be more effective than cisplatin in patients who received prior platinums is cisplatin resistance. The study cites this resistance as a reason that alternative platinums should be considered for women with metastatic or recurrent cervical cancer.
Ryo Kitagawa, MD, is an oncologist in the Department of Gynecology and Obstetrics, NTT Medical Center, Tokyo.
Abstract of the original JCO article.
PDF of the original JCO article.
Kitagawa R, Katsumata N, Shibata T, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase iii trial JCOG0505. J Clin Oncol. Epub 2015 March 2.
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@ 2014 American Society of Clinical Oncology