Alternatives to chemotherapy and radiotherapy as adjuvant treatment for lung cancer

Because adjuvant chemotherapy has resulted in only modest prolongation of survival for patients with lung cancer, investigators have turned to the evaluation of alternative treatment strategies for this patient population. Immunotherapy with Bacillus Calmette Guerin, Corynebacterium parvum, and levamisole has been evaluated in several prospective randomized trials, and no study has shown a statistically significant difference in overall survival. Interferon has been evaluated in three trials of adjuvant therapy after response to chemotherapy for small cell lung cancer. Different interferon preparations were used, but none of the trials showed a significant prolongation of survival. The retinoids have been evaluated as adjuvant treatment after complete resection of stage IN-SCLC. One trial showed a reduction in second primary tumors, and in particular, tumors to tobacco smoking in patients treated with retinyl palmitate. A second trial using 13-cis retinoic acid is ongoing in North America. In the last decade, several inhibitors of angiogenesis have been identified, and they are now beginning to be evaluated in the clinical setting. The National Cancer Institute of Canada Clinical Trials Group and the European Organization for Research and Treatment of Cancer have initiated a study of adjuvant marimastat, a metalloproteinase inhibitor, for patients who have responded to induction chemotherapy for small cell lung cancer. This is the first adjuvant antiangiogenesis factor trial to be initiated for any tumor type. Other investigational agents which are currently undergoing Phase I and Phase II testing include monoclonal antibodies which may inhibit tumour cell growth by binding to growth factors, or which may be conjugated to toxins or chemotherapeutic agents which result in tumour cell death. In the last decade, we have witnessed an explosion in our knowledge and understanding of the regulation of normal and neoplastic cell growth at the molecular level. It remains only speculative at this time as to whether manipulation of abnormal genes in malignant cells will be clinically possible, and whether treatment of this sort may be applied in an adjuvant setting.