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: Platinum-based doublets are standard of care for advanced non-small-cell lung cancer (NSCLC). The combination of docetaxel and oxaliplatin has shown acceptable toxicity and encouraging activity. This phase II study aimed to determine the safety and efficacy of this doublet with bevacizumab as first-line treatment for stage IIIB/IV NSCLC. Newly diagnosed patients ≥18 years with histologically proven non-squamous NSCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 received six 21-day cycles of docetaxel, oxaliplatin, and bevacizumab followed by single-agent bevacizumab for a total of 1 year. Primary efficacy end point was radiographically documented progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), time to treatment failure, and safety. Fifty-three patients were enrolled. Median age was 62.0 years, 71.7 % male, 79.2 % Caucasian. A total of 88.7 % had stage IV or recurrent disease; 94.3 % adenocarcinoma; and 94.3 % ECOG PS 0 or 1. Efficacy results are as follows: median PFS 5.6 months, ORR 30.2 % (complete response 1.9 %, partial response 28.3 %); 37.7 % stable disease; and OS 14.0 months. At least one adverse event (AE) was reported in all patients (n = 52); 98.1 % of AEs were treatment related. The most common treatment-emergent grade ≥3 AEs were neutropenia (15.4 %), diarrhea (13.5 %), and fatigue (11.5 %). A serious AE was present in 32.7 %; the most common were pneumonia (7.7 %) and abdominal pain (5.8 %). Dehydration, diarrhea, febrile neutropenia, sepsis, and supraventricular tachycardia each occurred in 3.8 %. The addition of bevacizumab to docetaxel/oxaliplatin is effective with an acceptable safety profile in patients with chemotherapy-naïve advanced NSCLC.Cancer Chemotherapy and Pharmacology 09/2013; 72(5). DOI:10.1007/s00280-013-2301-z · 2.57 Impact Factor