- Email: [email protected]
The Lung Cancer Study Group Experience
Adjuvant Therapy for Resectable Lung Cancer Chairman: Nasi Martini, M.D., F.C.C.P.
The Lung cancer StUdy Group Experience Robert] Ginsberg, M.D., F.C.C.P., University ofToronto, Toronto
T
he Lung Cancer Study Group was formed in 1976 to evaluate adjuvant treatment in surgically resected lung cancer patients. This cooperative group involves University centers in the United States and Canada, supported by grants from the National Institutes of Health. Since the first patient was entered in 1977, nearly 2,000 patients have been placed on protocols. Eleven different protocols have been developed, 5 of which are completed. The 6 other protocols are still entering patients. Common to all studies is accurate intraoperative surgical staging according to a modified American Joint Committee staging map, and accurate pathologic staging confirmed by a Pathology Reference Center, As well as studying the effects of adjuvant therapy on survival, prognostic factors, patterns of recurrence, pathologic correlations, and survival according to T and N status, have been analyzed. We have evaluated immunotherapy, chemotherapy and radiation therapy as adjuvants to surgical resection. Our initial protocol (LeSG 771)demonstrated that postoperative adjuvant intrapleural BCG following complete resection of stage I lung cancer showed no greater survival benefit, alteration of disease-free survival or patterns of recurrence, than an intrapleural placebo (saline). Over 400 patients were entered into this study. In patients with completely resected stage II and stage III adenocarcinoma and large cell undifferentiated carcinoma, we compared postoperative chemotherapy, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin) and cis-platin (CAP), versus adjuvant immunotherapy consisting of postoperative intrapleural BCG and orallevamisole (LeSG 772). This study, with over 100 entries, has been completed and demonstrates Significant prolongation of disease-free survival and overall survival in patients receiving CAP chemotherapy. Patients with completely resected stage II and stage III squamous cell carcinoma of the lung were randomized to receive postoperative radiotherapy (5,000 rads over 5 weeks), or no further treatment (LeSG 773).This study has now been terminated with over 200 patients entered. The only difference between the 2 groups is a significant reduction in locoregional recurrence in that group receiving postoperative radiotherapy. TIme to recurrence and overall survival do not appear to have been affected by the adjuvant radiotherapy. Over 150·patients with incompletely resected lung cancer (microscopic or macroscopic) were randomized to receive radiotherapy alone, or postoperative CAP chemotherapy plus radiotherapy (LeSG 791). There has been a significant survival benefit and disease-free survival in those patients receiving the combination chemoradiotherapy after incomplete resection. 3428
Other ongoing studies include: postoperative CAP chemotherapy versus no further therapy in completely resected TiN o and TiNl lung cancer (LCSG 801), limited resection versus lobectomy in patients with peripheral TlNo lesions (LeSG 821), and patients with T3No tumors involving the chest wall and after complete resection are randomized to receive postoperative radiation therapy versus no further treatment (LCSG 841). In addition to these randomized studies, a single pilot study has just been completed. In this study, patients with technically unresectable N2 disease were treated with preoperative CAP chemotherapy and mediastinal radiation therapy. If a complete or partial response occurred, thoracotomy and attempted resection was done (LCSG 831). Over 30 patients in this pilot study were entered. The results are presently being analyzed. Finally, the role of adjuvant surgical therapy in limited small cell lung cancer is being evaluated in a prospective randomized trial, comparing chemotherapy consisting of cytoxan, Adriamycin and vincristine with consolidation mediastinal and prophylactic cranial irradiation versus a similar protocol, with the addition of surgical resection of the primary disease after induction chemotherapy and prior to radiation therapy (LeSG 832). The Lung Cancer Study Group has demonstrated no advantage to postoperative immunotherapy in the treatment of surgically resected lung cancer. There are small but encouraging and significant improvements in patterns of recurrence, disease-free survival, and overall survival in certain subsets of non-small cell lung cancer with the use of adjuvant radiotherapy and chemotherapy. REFERENCES
Gail M, et al (Lung Cancer Study Group). Early side effects of intrathoracic BCG therapy in patients with non-small cell stage I lung cancer. Cancer Immunol Immunother 1981; 10:129-37 Mountain C, Gail M. Surgical adjuvant intrapleural BCG treatment for stage I non-small cell lung cancer-Preliminary report of the National Cancer Institute Lung Cancer Study Group. J Thorac Cardiovasc Surg 1981; 82:649-57 Wright ~ Feld R, Mountain C, Cooper J, Eagan R, Ginsberg RJ, et ale A prospective double-blind clinical trial of intrapleural bacillus calmette guerin (BCG) in patients with stage I non-small cell lung cancer (NSCLC). Adjuvant Therapy of Cancer III New York: Grune & Straton, 1981 Lung Cancer Study Group. Surgical adjuvant therapy in resectable stage IIIIII adenoca and large cell undiff Ca of the lung (meeting abstract). Fourth International Conf on the Adjuvant Therapy of Cancer, 21-24 March, 1984. Tucson: University of Arizona Cancer Center, 1984 Gail MH, Eagan In: Feld R, Ginsberg RJ,et ale Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group. Cancer 1~; 54 Weisenberger 1: et al (for the Lung Cancer Study Group). Recurrence patterns in resected stage IIIIII epidermoid lung cancer. Proc ASCO 232, 1984;C-909 Holmes EC, Egan RT (for the Lung Cancer Study Group). Surgical adjuvant therapy of resectable stage IIIIII. Adenocarcinoma and large cell undifferentiated carcinoma of the lung. Proc ASCO 1984; C-860-220
Lad 1: Weisenberger 'I: Adjuvant therapy of incompletely resected non-small cell bronchogenic carcinoma. Proceedings ASCO 4: 179 (C697) IV Wortd Conference on LungCancer
The Lung cancer StUdy Group Experience Robert] Ginsberg, M.D., F.C.C.P., University ofToronto, Toronto
T
he Lung Cancer Study Group was formed in 1976 to evaluate adjuvant treatment in surgically resected lung cancer patients. This cooperative group involves University centers in the United States and Canada, supported by grants from the National Institutes of Health. Since the first patient was entered in 1977, nearly 2,000 patients have been placed on protocols. Eleven different protocols have been developed, 5 of which are completed. The 6 other protocols are still entering patients. Common to all studies is accurate intraoperative surgical staging according to a modified American Joint Committee staging map, and accurate pathologic staging confirmed by a Pathology Reference Center, As well as studying the effects of adjuvant therapy on survival, prognostic factors, patterns of recurrence, pathologic correlations, and survival according to T and N status, have been analyzed. We have evaluated immunotherapy, chemotherapy and radiation therapy as adjuvants to surgical resection. Our initial protocol (LeSG 771)demonstrated that postoperative adjuvant intrapleural BCG following complete resection of stage I lung cancer showed no greater survival benefit, alteration of disease-free survival or patterns of recurrence, than an intrapleural placebo (saline). Over 400 patients were entered into this study. In patients with completely resected stage II and stage III adenocarcinoma and large cell undifferentiated carcinoma, we compared postoperative chemotherapy, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin) and cis-platin (CAP), versus adjuvant immunotherapy consisting of postoperative intrapleural BCG and orallevamisole (LeSG 772). This study, with over 100 entries, has been completed and demonstrates Significant prolongation of disease-free survival and overall survival in patients receiving CAP chemotherapy. Patients with completely resected stage II and stage III squamous cell carcinoma of the lung were randomized to receive postoperative radiotherapy (5,000 rads over 5 weeks), or no further treatment (LeSG 773).This study has now been terminated with over 200 patients entered. The only difference between the 2 groups is a significant reduction in locoregional recurrence in that group receiving postoperative radiotherapy. TIme to recurrence and overall survival do not appear to have been affected by the adjuvant radiotherapy. Over 150·patients with incompletely resected lung cancer (microscopic or macroscopic) were randomized to receive radiotherapy alone, or postoperative CAP chemotherapy plus radiotherapy (LeSG 791). There has been a significant survival benefit and disease-free survival in those patients receiving the combination chemoradiotherapy after incomplete resection. 3428
Other ongoing studies include: postoperative CAP chemotherapy versus no further therapy in completely resected TiN o and TiNl lung cancer (LCSG 801), limited resection versus lobectomy in patients with peripheral TlNo lesions (LeSG 821), and patients with T3No tumors involving the chest wall and after complete resection are randomized to receive postoperative radiation therapy versus no further treatment (LCSG 841). In addition to these randomized studies, a single pilot study has just been completed. In this study, patients with technically unresectable N2 disease were treated with preoperative CAP chemotherapy and mediastinal radiation therapy. If a complete or partial response occurred, thoracotomy and attempted resection was done (LCSG 831). Over 30 patients in this pilot study were entered. The results are presently being analyzed. Finally, the role of adjuvant surgical therapy in limited small cell lung cancer is being evaluated in a prospective randomized trial, comparing chemotherapy consisting of cytoxan, Adriamycin and vincristine with consolidation mediastinal and prophylactic cranial irradiation versus a similar protocol, with the addition of surgical resection of the primary disease after induction chemotherapy and prior to radiation therapy (LeSG 832). The Lung Cancer Study Group has demonstrated no advantage to postoperative immunotherapy in the treatment of surgically resected lung cancer. There are small but encouraging and significant improvements in patterns of recurrence, disease-free survival, and overall survival in certain subsets of non-small cell lung cancer with the use of adjuvant radiotherapy and chemotherapy. REFERENCES
Gail M, et al (Lung Cancer Study Group). Early side effects of intrathoracic BCG therapy in patients with non-small cell stage I lung cancer. Cancer Immunol Immunother 1981; 10:129-37 Mountain C, Gail M. Surgical adjuvant intrapleural BCG treatment for stage I non-small cell lung cancer-Preliminary report of the National Cancer Institute Lung Cancer Study Group. J Thorac Cardiovasc Surg 1981; 82:649-57 Wright ~ Feld R, Mountain C, Cooper J, Eagan R, Ginsberg RJ, et ale A prospective double-blind clinical trial of intrapleural bacillus calmette guerin (BCG) in patients with stage I non-small cell lung cancer (NSCLC). Adjuvant Therapy of Cancer III New York: Grune & Straton, 1981 Lung Cancer Study Group. Surgical adjuvant therapy in resectable stage IIIIII adenoca and large cell undiff Ca of the lung (meeting abstract). Fourth International Conf on the Adjuvant Therapy of Cancer, 21-24 March, 1984. Tucson: University of Arizona Cancer Center, 1984 Gail MH, Eagan In: Feld R, Ginsberg RJ,et ale Prognostic factors in patients with resected stage I non-small cell lung cancer. A report from the Lung Cancer Study Group. Cancer 1~; 54 Weisenberger 1: et al (for the Lung Cancer Study Group). Recurrence patterns in resected stage IIIIII epidermoid lung cancer. Proc ASCO 232, 1984;C-909 Holmes EC, Egan RT (for the Lung Cancer Study Group). Surgical adjuvant therapy of resectable stage IIIIII. Adenocarcinoma and large cell undifferentiated carcinoma of the lung. Proc ASCO 1984; C-860-220
Lad 1: Weisenberger 'I: Adjuvant therapy of incompletely resected non-small cell bronchogenic carcinoma. Proceedings ASCO 4: 179 (C697) IV Wortd Conference on LungCancer