Clinical Newswire

Cis-platinum, Pemetrexed and Bevacizumab (CPBev) first-line therapy is safe and efficacious for locally advanced or metastatic adenocarcinoma of the lung

James Bestilny

01/May/10

Clinical Newswire, May 1, 2010 (Geneva, Switzerland) - Two-drug combination regimens containing platinum salts have been the standard therapy for patients with stage IIIB and IV non-small cell lung cancer (NSCLC), regardless of tumor histologic sub-type. Two new antitumour agents, bevacizumab, a monoclonal antibody active against vascular endothelial growth factor (VEGF), and pemetrexed, an inhibitor of thymidalate synthase and other folate-dependent enzymes, have recently been shown to have selective efficacy in advanced NSCLC patients with particular histological tumor subtypes, and to improve median survival to over 12 months. A study presented at the 2nd European Lung Cancer Conference in Geneva, Switzerland, by Roberto Bordonaro, MD, tested the safety and efficacy of both these agents when combined with cisplatinum (CPbev regimen) in patients with stage IIIB and IV NSCLC.

This was a phase II study of patients (age $B!f(B18; median 57; range 36-77 years) that were chemotherapy-naive with histologically confirmed non-squamous NSCLC in advanced (III/B or IV) stage with less than one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Testing was initially performed on 15 patients, 14 with adenocarcinoma and one with bronchiolo-alveolar carcinoma (stage III/B (n=3) and stage IV (n=12)), with study termination ensuing if 5 or fewer patients responded and expansion of the study to 32 patients if > 6 responded. All patients had a PS-ECOG/WHO of 0 or 1, adequate bone marrow reserves and organ function, and a creatinine clearance $B!f(B45 ml/min calculated with the standard Cockroft-Gault formula. Exclusion criteria included the presence of brain metastasis, radiological signs of infiltration of large vessels, a history of hemoptysis and/or hemorragic diathesis or coagulopathy, and regular use of anticoagulant drugs or medically uncontrolled hypertension. The primary end-points were efficacy, as defined by percent clinical response, and safety. Secondary end-points included progression-free-survival (PFS) and overall survival (OS).

The CPbev regimen consisted of cis-platinum (75 mg p.s.m.) together with pemetrexed (500 mg p.s.m.) and bevacizumab (7.5 mg/kg) administered intravenously on day 1 and repeated every three weeks. Vitamin supplementation was initiated from day 1 of the first cycle and G-CSF was administered only after the first cycle. Instrumental restaging (mandatory CT-scan and second-level examinations by MRI or Positron-Emission-Tomography in select cases) was performed after the third and sixth cycles of therapy. Patients that demonstrated a clinical response received three or more additional cycles of therapy.

To date, 74 CPBev cycles have been administered. Thirteen of the 15 patients enrolled in the first phase of the study completed at least six cycles of therapy and were evaluable for clinical response. Partial response was observed in 7 patients, while 4 exhibited stable disease and 2 progressive disease.

The most common adverse events were grade 1 (G1) or grade 2 (G2) and included G1 proteinuria (25.6 %), G 1 -2 anemia (37.8%), hepixastis (14.8 %), emesis (33.7%), hypertension (7.2%). Six cases of extra-hematological toxicities of grade 3 or higher were observed. Two patients experienced grade 3 emesis that required supplementation with antiemetic medications; another patient experienced a symptomatic cardiac failure immediately after the fifth cycle of chemotherapy, with FEV falling to 40%. In this patient, treatment was discontinued and the patient rapidly recovered after initiation of cardiological therapy. There were 5 (6.7%) episodes of grade 3 neutropenia, which the authors speculated may be the result of G-CSF administration which was performed in all the patients after the first cycle of therapy.

The authors conclude that the CPBev regimen is a safe and manageable regimen for patients with stage IIIB and IV NSCLC. On the basis of the results registered to date in this ongoing clinical trial, enrollment will increase to 32 patients.