Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.

Abstract

In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of Thoracic Radiotherapy Combined with Chemotherapy in Limited Stage Small Cell Lung Cancer (SCLC)

“…All irradiated patients showed a remarkable improvement of survival time of 12.8 months compared to the non-irradiated group with 9.7 months (p = 0.02). These results are comparable to the results of Perry and Ihde [6,19], but in different studies results concerning survival time and disease-free survival still have not been convincing [8,20,21]. The two year-survival rate was 15% for all groups, 19% for the irradiated compared to 5% to the non-irradiated group.…”

Experimental and clinical studies alternating chemotherapy and radiotherapy

“…For example, in the randomized trial by Perry et al [25], the failure-free survival rates at 2 years are, respectively, 20% and 8% in the arms treated by RT + CT or CT alone. However, this beneficial effect is generally modest; moreover, it is not observed when the delivery of CT and RT is sequential, such as in the Southwest Oncology group trial [26]. In that study, the addition of RT did not improve survival once CR had been achieved by induction C'T; this was probably due to the absence of CT for 7.5 weeks in the latter arm as discussed above.…”

Radiation Therapy in Management of Small-Cell Lung Cancer

“…In this study, patients achieving a partial response after chemotherapy were randomized to pre-versus post-chemotherapy volume irradiation arms. Outcomes of this benchmark study did not indicate any superiority for pre-chemotherapy volume irradiation arm over post-chemotherapy irradiation counterpart, in terms of neither local/regional nor survival rates (Kies et al, 1987). This issue has latter been investigated by Liengswangwong et al in a retrospective analysis.…”