BONE MARROW-SPARING AND PREVENTION OF ALOPECIA BY AS1O1 IN NON-SMALL-CELL LUNG-CANCER PATIENTS TREATED WITH CARBOPLATIN AND ETOPOSIDE

Purpose: The aim of this study was to evaluate the ability of the immu nomodulator AS101 to prevent chemotherapy-induced neutropenia and thro mbocytopenia and thus allow patients to receive full-dose antineoplast ic agents according to protocol design, We also aimed to determine the production level of various hematopoietic growth factors in treated p atients, Patients and Methods: This study of 44 unresectable or metast atic non-small-cell lung cancer (NSCLC) patients was an open-label pro spective randomized study of standard chemotherapy alone versus chemot herapy plus AS101. Each patient received carboplatin (300 mg/ m(2) int ravenously [IV]) on day 1 of ct 28-day cycle, and etoposide (VP-16) (2 00 mg/m(2) orally) on days 3, 5, and 7 of each cycle, AS101 was admini stered at 3 mg/m(2) three times per week starting 2 weeks before chemo therapy, Results: AS101, which manifested no major toxicity, significa ntly reduced neutropenia and thrombocytopenia and thus allowed all tre ated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 si gnificantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as refl ected by the higher overall response rate compared with the chemothera py-alone arm. Interestingly, AS101 treatment also significantly preven ted chemotherapy-induced alopecia. These effects correlate with the ab ility of AS101-treated patients to increase significantly the producti on of colony-stimulating factors (CSFs) interleukin-1 alpha (Il-lcr) a nd IL-6. Conclusion: AS101 has significant bone marrow (BM)-sparing ef fects and prevents hair loss in chemotherapy-treated patients, with mi nimal overall toxicity, These effects are probably due to increased pr oduction of IL-1 alpha, IL-6, and granulocyte-macropherge (GM)-CSF. (C ) 1995 by American Society of Clinical Oncology.