A Prospective, Feasibility Study of S-1 and Carboplatin for Patients with Pulmonary Fibrosis (PF) and Advanced Non-Small-Cell Lung Cancer (NSCLC)

ABSTRACT Background PF is commonly concomitant disorder with lung cancer. Because PF sometimes deteriorates and results unfavorable clinical course, patients with PF are excluded from most cancer clinical trials. S-1 is a novel active oral fluoropyrimidine anticancer agent consisting of tegafur, gimeracil, and oteracil potassium. Although most of the anti-cancer agents have pulmonary toxicity, post marketing surveillance reported that S-1 has lower pulmonary toxicity incidence. We have conducted a feasibility study of S-1 and carboplatin combination for patients with advanced or ineligible for other treatment modality of NSCLC patients. Methods Patients with histologically or cytologically confirmed NSCLC, clinically diagnosed pulmonary fibrosis, aged 80 years old or younger, performance status 0–2 and chemo-naive were eligible for the study. Carboplatin (AUC 5) was administered on day 1 and S-1 (80 mg/m2/day) on day 1 to 14 for four to six cycles. End points were response rate, common safety profiles and effect to PF. Results From March 2009 to December 2011, 21 patients (19 males/2 females, median age 67 years old, ranged 55 to 77, 10 adenocarcinoma, 10 squamous, 1 adenosquamous, stage IIA: 1, IIIA: 3, IIIB: 9, IV: 4, recurrence: 4) were enrolled. All patients had moderate or severe PF. Treatment delivery; 1 cycle: 3 patients, 2: 3 patients, 3: 3 patients, 4: 10 patients, 5; 1 patient, 6: 1 patients. Partial responses were observed in 7 patients (RR; 33%). The median progression-free survival duration was 4.0 months, and the median overall survival duration in 10.4 months. During the treatment, two patients experienced moderate deterioration of pulmonary fibrosis, one experienced infectious pneumonia—all three patients recovered from the event. There was no treatment related death. Besides pulmonary toxicity, most common adverse events were myelotoxicities. Conclusions This is the first trial of S-1 and carboplatin combination for patients with PF and NSCLC. The study revealed S-1 and carboplatin combination was feasible and active even in patients with PF and NSCLC who are usually excluded from cancer clinical trials.