If the patient is treated with platinum, the next question is whether the platinum should be treated alone or in combination with another second-line drug. Two phase II randomized trials provide important evidence that platinum-based combination chemotherapy is superior to platinum alone in the treatment of recurrent ovarian cancer.
The design of the first reported trial (ICON-4) is complex, but it mainly compares the efficacy of single platinum and platinum plus paclitaxel. This trial revealed that the combination chemotherapy regimen improved both progression-free survival and overall survival. After 2 years of follow-up, the overall survival rate of carboplatin plus paclitaxel was significantly increased by 7% (57% vs 50%).Unfortunately, a significant improvement in survival must be accompanied by an increase in secondary neurotoxicity in the combined chemotherapy group compared with the monotherapy group (grade 2 to 3: 20% to 1%).The second randomized study compared carboplatin alone with carboplatin plus gemcitabine in the treatment of recurrent ovarian cancer. This study also showed that combination chemotherapy improved progression-free survival, but unlike previous ICON-4 results, the overall survival rate was not improved. Although there are some hypotheses to explain why this trial does not improve overall survival, the most likely reason is that many patients treated with carboplatin alone and carboplatin plus gemcitabine received advanced-step chemotherapy after the disease progressed, while patients in the ICON-4 study ended treatment. Only one theory has been proven that active third-line chemotherapy can have a statistically significant effect on survival, regardless of previous treatment.As speculated, there was no significant difference in severe neurotoxicity between the two groups (carboplatin plus gemcitabine and carboplatin) because gemcitabine itself had no neurotoxicity.A randomized phase I trial comparing the effects of carboplatin liposome doxorubicin with carboplatin plus paclitaxel is nearing completion and results will be available soon. These results can add effective combination chemotherapy for recurrent ovarian cancer to evidence-based clinical trials. A series of ineffective treatments for recurrent ovarian cancer have been reported in evidence-based clinical trials.
