Continuation of chemotherapy versus supportive care alone in patients with inoperable non-small cell lung cancer and stable disease after two or three cycles of MACC. Results of a randomized prospective study

Abstract

Recommendations concerning the continuation of chemotherapy in nonresponding patients with non-small cell lung cancer (NSCLC) and stable disease after the first chemotherapy test are empirical and often conflicting. Between 1984 and 1987, 116 inoperable NSCLC patients were treated with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC regimen). After two or three cycles of therapy, 74 patients were judged to have stable disease and assigned at random either to chemotherapy maintenance with the same regimen (38 subjects) or to chemotherapy discontinuation (36 subjects). The two study groups were comparable for all the major prognostic factors. Median time to progression was 26 weeks for the chemotherapy group compared to 24 weeks for the nonchemotherapy group (P = NS). Median survival was prolonged in the treatment arm (47 weeks) compared to nontreatment arm (30 weeks), which was statistically nonsignificant. A patient self-assessment of the quality of life revealed a significantly worse tolerance to therapy and a better physical condition in the chemotherapy group. Objective MACC toxicity was significant with two treatment-related deaths. This study failed to demonstrate sufficient therapeutic benefits to justify the increased cost and toxicity of continuing treatment in nonresponding NSCLC patients.

Maintenance Therapy for Advanced Non-small Cell Lung Cancer: Current Status, Controversies, and Emerging Consensus

“…However, prior studies in NSCLC have failed to show convincing clinical benefit as measured by overall survival advantage in patients treated with a prolonged course of chemotherapy (14)(15)(16)(17). Some of these initial studies were fraught with methodological flaws that either led to study redesign or post hoc adjustment of the power of the study to detect the anticipated survival differences (14).…”

“…However, prior studies in NSCLC have failed to show convincing clinical benefit as measured by overall survival advantage in patients treated with a prolonged course of chemotherapy (14)(15)(16)(17). Some of these initial studies were fraught with methodological flaws that either led to study redesign or post hoc adjustment of the power of the study to detect the anticipated survival differences (14). Of greater significance is the fact that some of the trials employed chemotherapy regimens that, in light of contemporary practice, will be considered too toxic for maintenance or prolonged therapy (14,15,17).…”

“…Some of these initial studies were fraught with methodological flaws that either led to study redesign or post hoc adjustment of the power of the study to detect the anticipated survival differences (14). Of greater significance is the fact that some of the trials employed chemotherapy regimens that, in light of contemporary practice, will be considered too toxic for maintenance or prolonged therapy (14,15,17). It is therefore no surprise that the majority of patients were unable or unwilling to receive the protocol-mandated maintenance therapy in a majority of the early maintenance trials conducted in patients with NSCLC.…”

Optimal Duration of Chemotherapy in Advanced Non-Small Cell Lung Cancer

“…In 1997, a consensus statement by American Society of Clinical Oncology recommended that chemotherapy in advanced stage NSCLC should not be extended beyond eight cycles [6]. These recommendations were based on the only trial completed at that time by Buccheri et al which compared non-platinum based chemotherapy after 2-3 cycles to continuous treatment [7]. No survival benefit was seen in continuous treatment.…”

Maintenance therapy for patients with advanced non-small cell lung cancer: Who to treat and how to treat?

“…Several trials showed no signifi cant diff erences in survival or quality of life (QoL) between patients undergoing a short or long-duration of combination chemotherapy [4,[9][10][11][12]. Th ese studies demonstrate that continuation of combination chemotherapy beyond a defi ned number of cycles did not provide additional benefi t, but it was associated with higher, clinically relevant toxicities.…”