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ABSTRACT: Currently, no effective treatments exist for non-small cell lung cancer (NSCLC) after failure of gefitinib therapy. Pre-clinical studies have demonstrated that gefitinib-resistant NSCLC cells are more sensitive to irinotecan than parental cells, and that combined administration of irinotecan and gefitinib has a synergistic additive effect. We conducted a phase I study to evaluate the combination of irinotecan and gefitinib as a therapeutic option for NSCLC patients with progressive disease (PD) after initial gefitinib treatment.
Eligibility criteria included histologically confirmed NSCLC, age range of 20-74 years, refractory to or relapsed after gefitinib treatment, one or more previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and informed consent. Patients were treated with irinotecan on days 1 and 15, and treated daily with gefitinib from day 2 every 4 weeks. The treatment was continued until disease progression. The gefitinib dose was fixed at 250 mg. Irinotecan dosing started at 50 mg m(-2) and was escalated in patients by 25 mg m(-2) increments up to a maximum dose of 150 mg m(-2).
Twenty-seven patients were enrolled: male/female=14/13; median age=60 (45-75); histology, adenocarcinoma/non-adenocarcinoma=25/2; performance status 0-1/2=19/8; previous response to gefitinib, partial response/stable disease/PD=21/2/4. Dose-limiting toxicities were observed in 2 patients at level 3. Maximum tolerated dose was not determined, and the full dose of irinotecan could be combined with the full dose of gefitinib. The disease control rate (DCR) and response rate (RR) were 69.2 and 26.9%, respectively. For 12 patients at level 5 (the recommended phase II dose), the DCR and RR were 75.0% and 41.7%, respectively. The median treatment cycles were 4; median time to treatment failure, 57 days (95% confidence interval (CI), 32-82 days); median overall survival, 244 days (95% CI, 185-303 days); and 1-year survival rate, 32.6%.
The combination of irinotecan and gefitinib was well tolerated and potentially beneficial for NSCLC patients failing initial gefitinib monotherapy.
British Journal of Cancer 09/2011; 105(8):1131-6. · 5.04 Impact Factor
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F Ohyanagi,
N Yamamoto, A Horiike,
H Harada,
T Kozuka,
H Murakami,
K Gomi,
T Takahashi,
M Morota,
T Nishimura,
M Endo,
Y Nakamura,
A Tsuya,
T Horai,
M Nishio
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ABSTRACT: To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC).
Eligible patients were 20-74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0-1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m(-2) on day 1) and S-1 (orally at 40 mg m(-2) per dose, b.i.d., on days 1-14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions.
Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1-96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively.
This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.
British Journal of Cancer 08/2009; 101(2):225-31. · 5.04 Impact Factor
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ABSTRACT: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR, HER1/ErbB1) tyrosine kinase, has been shown to have clinical activity against non-small-cell lung cancers (NSCLCs), especially in women nonsmokers with adenocarcinomas. The aim of the present study was to clarify the relationship between androgen levels and gefitinib treatment in patients with advanced NSCLCs. Sera from 67 cases (36 men and 31 women) were obtained pretreatment and during treatment with gefitinib monotherapy (days 14-18) for examination of testosterone, dehydroepiandrosterone sulphate (DHEA), and dehydroepiandrosterone sulphate (DHEAS) levels. Testosterone and DHEA during treatment were significantly lower than the pretreatment values in both women and men, and the DHEAS levels during treatment were also significantly lowered in women. Gefitinib treatment significantly suppressed androgen levels, especially in women who had no smoking history. In addition, hormone levels in women responding to gefitinib were significantly lower during the treatment than in women who did not respond. Gefitinib-associated decrease in serum androgen levels may play a role in its clinical efficacy.
British Journal of Cancer 06/2005; 92(10):1877-80. · 5.04 Impact Factor
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ABSTRACT: The recommended phase II dose of paclitaxel 180 mg m(-2) given as a 3-h infusion followed by nedaplatin 100 mg m(-2) in a 1-h infusion every 3-4 weeks was determined in 52 chemo-naive patients with unresectable squamous cell carcinoma (SCC), with a promising response rate for lung SCC of 55%.
British Journal of Cancer 04/2004; 90(6):1125-8. · 5.04 Impact Factor
