High‐dose, multiple‐alkylator chemotherapy with autologous bone marrow reinfusion in patients with advanced non‐small cell lung cancer

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high‐dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m² over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m² and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I‐II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high‐dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.