A feasibility/phase II study of gemcitabine (G) and split dose cisplatin (C) in advanced or metastatic non-small cell lung cancer (NSCLC) in an outpatient setting

Abstract

17048 Background: This is a feasibility/phase II trial with GC on a 21-day cycle, with G and C split between d1, 8. Split dose C allowed administration in an outpatient setting. Objectives: To document the toxicity and define the objective response rate; and determine progression free and overall survival. Methods: Pts with stage III/IV NSCLC received: G/C 1250/40mg/m2 (G and C given on d1, 8 every 3 wks). Eligibility: ECOG PS 0–2, adequate bone marrow/liver function, calculated GFR > 50 ml/min. Results: 56 pts enrolled, all evaluable for toxicity; 47 evaluable for response; 4 patients too early for response assessment and 5 patients did not complete 1 cycle of chemotherapy. Characteristics: 70% male, median age 66 yrs (41–77), 25% GFR 50- 60 ml/min, 62% Stage IV. Radiotherapy was allowed after completing chemotherapy. 165 cycles have been delivered. Cycles with hematological toxicity: Grade 3: 5 anaemia, 17 neutropenia, 6 thrombocytopenia; Grade 4: 7 neutropenia, 4 thrombocytopenia. There were 3 episodes of febrile neutropenia. Cycles with non-hematological toxicity: Grade 4: 1 myocardial infarction (MI), 1 gastrointestinal (GI) bleed, 1 pulmonary embolism, 1 stroke; Grade 3: 3 nausea, 1 deep vein thrombosis, 4 chest infection, 1 hypomagnesemia; Grade 2: 3 renal toxicity, 2 seizure, 1 hypomagnesemia. Five cycles were deferred due to grade 4 neutropenia; 2 for renal toxicity (in one patient with diabetes and hypertension renal function declined after 1 cycle necessitating discontinuation of chemotherapy). 2 deaths occurred on treatment: 1 MI (patient with a previous history of MI); 1 GI bleed (on aspirin). Overall ITT RR was 33% (17/52: 1 CR+ 16 PR) (36% [17/47] for assessable pts). Median survival is 310-days. 1- year survival rate is 38%. Conclusion: G plus C in a 21-day schedule is active and well tolerated in an outpatient setting. This modified regimen with C split between d1 and d8, and, eligibility criteria of GFR as low as 50mls/min widens the spectrum of patients receiving cisplatin-based chemotherapy. Phase III trial is warranted. [Table: see text]