Irinotecan and oxaliplatin combination as the first-line treatment for patients with advanced non-small cell lung cancer
ABSTRACT BackgroundWe conducted a prospective phase II trial of IrOx in patients with advanced non-small cell lung cancer to evaluate the efficacy
Patients and methodsPatients with histologically or cytologically proven non-small cell lung cancer (NSCLC), aged ≥18 years, Eastern Cooperative
Oncology Group performance status 0–1, at stage IIIB (pleural effusion)/IV or with recurrent disease not suitable for primary
surgical treatment, with no palliative chemotherapy or radiotherapy to the chest or immunotherapy or biologic therapy, the
presence of measurable disease by RECIST, and who had given signed written informed consent, were eligible. Treatment consisted
of irinotecan 65 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 1, repeated every 3 weeks.
ResultsA total of 18 patients were enrolled in June and August 2007, the median age was 59 years (47–73). In total, 71 cycles were
administered with a median of 4 cycles per patient (range, 1–6 cycles) and 18 patients were evaluable for treatment response.
An independent review of tumor responses gave an overall response rate of 27.7% (CR: 0, PR: 5/18; 95% CI, 7–48.4%) by intent-to-treat
analysis. The median overall survival of all patients was 14 months and the median time-to-progression was 4.2 months (95%
CI, 1.959–6.441). The most common grade 3/4 toxicities were diarrhea (7% of all cycles) and neutropenia (5.6% of all cycles).
Grade 3 peripheral neuropathy occurred in one patient and one patient died due to sepsis.
ConclusionThis study suggests that IrOx combination therapy has moderate activity with a tolerable toxicity profile. However, it was
not warranted to evaluate further this regimen as first-line treatment for patients with advanced or metastatic NSCLC using
the current dosages and schedule.
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ABSTRACT: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m(2)) after CPT-11 administration on day 1. Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32. 7% ) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to < or = 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.Journal of Clinical Oncology 09/1999; 17(9):2710-20. · 18.04 Impact Factor
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ABSTRACT: The aim of this study was to determine the maximum-tolerated dose (MTD) and the recommended dose of irinotecan and oxaliplatin with a fixed 5-fluorouracil (5-FU)/leucovorin (LV) regimen in patients with metastatic solid tumors. The trial was designed to evaluate escalating doses of oxaliplatin and irinotecan, starting at 60 mg/m2 and 90 mg/m2, respectively, given at day 1 with the full-dose LV5FU2 regimen, given on days 1 and 2 as follows: folinic acid 200 mg/m2 followed by 5-FU 400 mg/m2 bolus and 600 mg/m2 22 h continuous infusion, every 2 weeks. The second cohort of patients was treated at the recommended dose for oxaliplatin and irinotecan with the simplified LV5FU regimen: on day 1, a 2-h infusion of folinic acid (400 mg/m2), followed by a 10-min intravenous bolus of 5-FU (400 mg/m2), followed by a continuous infusion of 5-FU (2400 mg/m2) over 46 h. Thirty-four patients were treated at the following dose levels (oxaliplatin/irinotecan mg/m2): 60/90, 60/120, 85/120, 85/150, 85/180, 85/200 and 85/220 and seven patients were treated at the recommended dose with the simplified LV5FU scheme. The MTD was reached at dose level 85/220 mg/m2 but the recommended dose chosen for the second step was 85/180 mg/m2 to keep a better compliance with the biweekly schedule. Main grade 3/4 toxicities per patient included the following: neutropenia in 78% (febrile episodes in 12%), diarrhea in 27%, nausea/vomiting in 24% and peripheral neuropathy in 37% (Lévi's scale). Antitumor activity was observed at almost all dose levels. Most objective responses were observed in digestive malignancies, since 10 out of 11 were obtained in five colorectal cancers, two pancreatic cancers, two cholangiocarcinoma and one gastric cancer. The recommended dose for the triple association is 85/180 mg/m2 of oxaliplatin and irinotecan, respectively, with LV5FU2 or simplified LV5FU. The antitumor activity in gastrointestinal malignancies should be evaluated in phase II studies in different tumor types.Annals of Oncology 04/2003; 14(3):481-9. · 7.38 Impact Factor
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ABSTRACT: To determine efficacy and toxicity of two pemetrexed-based regimens in chemonaive patients with locally advanced or metastatic non-small cell lung cancer. Patients were randomly assigned to receive pemetrexed 500 mg/m(2) plus oxaliplatin 120 mg/m(2) (PemOx) or pemetrexed plus carboplatin AUC6 (PemCb). All drugs were given on day 1 of a 21-day cycle for up to six cycles. Folic acid and vitamin B(12) were given to all patients to minimize pemetrexed-related toxicities. Forty-one patients received PemOx and 39 received PemCb. Objective tumor response rates were 26.8% for PemOx patients (95% confidence interval, 14.2-42.9) and 31.6% for PemCb patients (95% confidence interval, 17.5-48.7). Median time to progression was 5.5 and 5.7 months, respectively, for PemOx and PemCb. Median overall survival times were 10.5 months for both treatment groups (range, <1 to >20 months). The 1-year survival rate was 49.9% for PemOx patients and 43.9% for PemCb patients. Common toxicity criteria grade 3 or 4 hematologic toxicities among PemOx patients were grade 3 or 4 neutropenia (7.3%), grade 3 thrombocytopenia (2.4%), and grade 3 anemia (2.4%). PemCb patients experienced grade 3 or 4 neutropenia (25.6%), grade 3 or 4 thrombocytopenia (17.9%), and grade 3 anemia (7.7%). Grade 3 vomiting occurred in three PemOx patients and grade 3 fatigue occurred in three PemCb patients. One grade 3 neurosensory toxicity occurred in the PemOx group. Three patients (PemOx 1 and PemCb 2) experienced febrile neutropenia. Efficacy measures for both regimens seem similar to the most effective chemotherapies for advanced non-small cell lung cancer (platinum combinations) with less hematologic and nonhematologic toxicity. Comparing either of these two regimens to platinum-based therapies in a large randomized trial is warranted.Clinical Cancer Research 02/2005; 11(2 Pt 1):690-6. · 7.84 Impact Factor