Retreatment of patients with the same chemotherapy: Implications for clinical mechanisms of drug resistance

Background: Patients who relapse after adjutant chemotherapy, or after attaining remission following treatment of advanced disease, are sometimes retreated with the same type of chemotherapy. The objective of the current review of published reports was to assess the probability of response to retreatment, and to examine evidence for transient rather than stable forms of clinical drug resistance. Methods: A Medline review of published clinical series where patients were retreated with the same chemotherapy that they had received previously. Results: We located 15 reports of patients with advanced disease who were retreated with the same chemotherapy following complete remission and subsequent relapse, and three reports where patients received the same chemotherapy that was given previously as adjuvant treatment for breast cancer. For patients with advanced disease the median time off-treatment was 48 weeks; response rates to retreatment using appropriate criteria were in the range of 18%-100% (median 51%), with a substantial proportion of second complete responses. For patients retreated after adjuvant chemotherapy for breast cancer the median interval between treatments was 84 weeks and the response rates were in the range of 40%-51%. Conclusions: With the caveat that this type of review is subject to publication bias, retreatment of patients who relapse after complete response to initial therapy, or after adjuvant therapy, is associated with a substantial probability of response. Together with evidence that more prolonged or intensive initial therapy rarely leads to more frequent or more prolonged responses, the current review suggests that some patients may develop transient resistance to chemotherapy.