G. Fantino

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2 : A pilot study

Stage IIIb non-small-cell lung cancer (NSCLC) has a poor prognosis. The median survival is approximately 6 months, and only 30% of patients are alive 1 year after diagnosis. The need for effective treatment is evident. The aim of this study was to evaluate whether the infusion of tumor-infiltrating lymphocytes (TILs), isolated from resected tumor, expanded in vitro and injected together with recombinant Interleukin-2, is feasible and may at least partially modify the poor prognosis in these patients. The infusion of TILs, derived from surgically resected NSCLC and expanded in vitro, together with subcutaneous (s.c.) injections of recombinant interleukin-2 (rIL-2) was attempted in a group of 11 patients. Treated patients were infused i.v. with in vitro expanded TILs (from 4 to 70 x 10(9) cells), and rIL-2 was injected s.c. at doses varying from 61 to 378 x 10(6) IU. Toxic side effects (fever and, in some cases, hypotension) were observed and limited the dose of rIL-2 infused. Follow-up was continued for 40 months. The mean survival time was 13.8 months. Three of five TIL-treated patients with residual disease have no evident disease after 1 year, and two of them are still alive and have no evidence of disease after 40 months. This pilot study suggests that the infusion of in vitro expanded TILs, derived from surgical samples, is feasible and seems to prolong overall survival and to control the residual disease in patients with advanced NSCLC.

Immunotherapy with the use of tumor-infiltrating lymphocytes and interleukin-2 as adjuvant treatment in stage III non-small-cell lung cancer: A pilot study

This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating does for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease.