A phase I–II study of bi-weekly gemcitabine and irinotecan as second-line chemotherapy in non-small cell lung cancer after prior taxane + platinum-based regimens

Purpose: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I–II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. Patients and methods: Patients with advanced NSCLC, WHO-performance status (PS) ≤ 2, prior taxane/platinum-based chemotherapy were eligible. Chemotherapy was administered in a dose-escalated fashion in subgroups of 3–6 patients until dose-limiting toxicity (DLT) was encountered as follows: CPT-11 150 or 180 mg/m² followed by GEM 1,200–1,800 mg/m², both on days 1 + 15, recycled every 28 days in four dose levels (DLs). Results: Forty-nine patients entered the phase I and II part of the study (phase I: 12–phase II: 37 + 3 at DL-3), and 40 patients were evaluable for a response in phase II and all for toxicity: median age, 61 years (range 36–74); PS, 1 (0–2); gender, 43 males/6 females—histologies; adenocarcinoma, 25; squamous, 20; large cell, 4. Metastatic sites included lymph nodes, 38; bone, 5; liver, 4; brain, 3; lung nodules, 14; adrenals, 13; other, 3. All patients had prior taxane + platinum-based treatment, and 42 patients had prior docetaxel–ifosfamide–cisplatin/or–carboplatin regimens. DLT was observed at DL-4 and included 2/3 cases with grade 3 diarrhea—1/3 of these with febrile neutropenia. The recommended DL for phase II evaluation was DL3: GEM, 1,500 + CPT-11—180 mg/m². Objective responses in phase II were PR, 6/40 [15%; 95% confidence interval (CI), 5–31%]; stable disease, 16/40 (40%; 95% CI, 21–53%); and progressive disease, 18/40 (45%; 95% CI, 28.5–62.5%). The median time-to-progression was 4 months (range 1–12) and median survival 7 months (range 1.5–42 +), while 1-year survival was 20%. Grade 3/4 neutropenia was seen in 18% of patients (6% grade 4) and 6% incidence of febrile neutropenia. No Grade 3/4 thrombocytopenia were seen, grade 3 diarrhea in 6% of patients and grade 2 in 15% of patients, while other grade 3 non-hematologic toxicities were never encountered. Conclusions: Bi-weekly GEM + CPT-11 is active and well tolerated in patients with advanced NSCLC failing prior taxane + platinum regimens, and represents an effective and convenient combination to apply in the palliative treatment of relapsed NSCLC particularly after failure of first-line docetaxel + platinum-based regimens.