Phase I/II study of weekly irinotecan and concurrent radiation therapy for locally advanced non-small cell lung cancer.
A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, surgically unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled. Irinotecan was administered as a 90 min intravenous infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose escalation was done in 15 mg m(-2) increments. Dose-limiting toxicity was defined as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or grade 4 haematologic toxicity according to the WHO criteria. Radiation was delivered to the primary tumour and regional lymph nodes (40 Gy), followed by a boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six eligible patients were evaluated for toxic effects and clinical outcome. Severe oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of the five patients given 60 mg m(-2) developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 45 mg m(-2) in the phase II study. The objective response rate was 76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose-limiting toxicities of weekly irinotecan combined with thoracic irradiation. The maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(-2) wk(-1), respectively. This combined therapy for locally advanced non-small cell lung cancer is promising and shows acceptable toxicity.
Takeda
K
K
Department of Pulmonary Medicine, Osaka City General Hospital, Osaka, Japan.
Negoro
S
S
Kudoh
S
S
Okishio
K
K
Masuda
N
N
Takada
M
M
Tanaka
M
M
Nakajima
T
T
Tada
T
T
Fukuoka
M
M
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D000077146:Irinotecan; D002166:Camptothecin