Dose escalation study of paclitaxel in combination with fixed-dose irinotecan in patients with advanced non-small cell lung cancer (JCOG 9807).
BACKGROUND
Both irinotecan (CPT) and paclitaxel (Pac) are effective against non-small cell lung cancer (NSCLC), and besides, preclinical studies have demonstrated an additive or synergistic interaction between camptothecin and taxane.


METHODS
We conducted a phase I/II study of combination chemotherapy consisting of Pac and CPT to determine qualitative and quantitative toxicities and efficacy of the combination against advanced NSCLC. We fixed the dose of CPT at 60 mg/m(2) and escalated the Pac dose in 10 or 20 mg/m(2) increments from a starting dose of 80 mg/m(2), and repeated the cycle every 2 weeks. Prophylactic G-CSF was also administered.


RESULTS
Between February 1999 and April 2001, 24 patients were registered in the study. None of the patients had a history of prior chemotherapy, but surgical resection had been performed in 3 of them. None of the patients experienced dose-limiting toxicity (DLT) up to and including level 6. At dose level 7 of Pac, 180 mg/m(2), 2 patients experienced DLT, that is grades 2 and 3 dyspnea due to pneumonitis. Another patient experienced grade 1 dyspnea due to pneumonitis. Neutropenia, diarrhea, and other toxicities were mild; however, we concluded that dose level 7 of Pac was the maximum-tolerated dose. An objective response was observed in 58.3%. The median survival time was 370 days, and the 1-year survival rate was 54.2%.


CONCLUSIONS
Pneumonitis was the DLT in this study, and Pac 160 mg/m(2) and CPT 60 mg/m(2) every 2 weeks are recommended for the phase II study. This combination shows appreciable activity against NSCLC.
Yamada
Kouzo
K
Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
Ikehara
Mizuki
M
Tanaka
Gaku
G
Nomura
Ikuo
I
Oshita
Fumihiro
F
Noda
Kazumasa
K
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011014:Pneumonia / Q000139:chemically induced; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin