Feasibility of cisplatin/pemetrexed with 15 mg/kg bevacizumab for the treatment of patients with advanced non-squamous non-small cell lung cancer

Abstract

Abstract. The aim of the present study was to retrospectively evaluate the feasibility of cisplatin/pemetrexed/bevacizumab (CPB) therapy at a bevacizumab (BEV) dose of 15 mg/kg as a first-line chemotherapeutic strategy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). A total of 31 consecutive patients with non-squamous NSCLC were treated with first-line chemotherapy of CPB at a BEV dose of 15 mg/kg at the National Kyushu Cancer Center (Fukuoka, Japan) between November 2009 and December 2011. Clinical characteristics, response rate (RR), progression-free survival (PFS) time, overall survival (OS) time and adverse events were retrospectively analyzed. The 31 patients exhibited a male:female ratio of 21:10 and a median age of 60 years (range, 38-76 years). In total, 5 patients were of clinical stage III and 26 patients were of stage IV, 15 had a performance status of 0 and 16 had a performance status of 1, and 29 patients were diagnosed with adenocarcinoma and 2 were diagnosed with adenosquamous carcinoma. The EGFR mutation status was positive (exon 19 deletion), wild-type and unknown in 3, 21 and 7 patients, respectively. A total of 28 patients (90.3%) received a minimum of four courses of CPB therapy. Hematological toxicities classified as grade III or higher included neutropenia (29.0%), anemia (3.2%) and thrombocytopenia (3.2%), however, no severe non-hematological toxicities were observed. Additionally, 22 patients (71.0%) exhibited a partial response and 9 (29.0%) exhibited stable disease, resulting in a RR of 71.0% [95% confidence interval (CI), . The median PFS and OS times were 8.4 months (95% CI, 7.9-9.0) and 28.5 months (95% CI, 26.4-30.6), respectively. Therefore, CPB therapy at a BEV dose of 15 mg/kg appears to be a feasible treatment strategy for patients with advanced non-squamous NSCLC. IntroductionAt present, the standard first-line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) is platinum doublet chemotherapy using a third-generation anticancer agent (1,2). Pemetrexed (PEM) is a novel metabolic antagonist capable of inhibiting multiple enzymes involved in folate metabolism that has been clinically introduced as an effective therapeutic agent in the treatment of NSCLC (3-5). Previously, the results of two phase III studies indicated the efficacy of PEM as a first-line therapy for advanced NSCLC (6,7). In the JMDB study, cisplatin (CDDP) plus PEM therapy was not determined to be inferior to CDDP plus gemcitabine (GEM) therapy in terms of the overall survival (OS), and the incidence of severe adverse events was significantly lower following CDDP plus PEM therapy (6). Furthermore, in a subgroup analysis according to histological type, the OS of patients with non-squamous NSCLC was significantly longer in the CDDP plus PEM therapy group compared with the CDDP plus GEM group. In addition, the effectiveness of PEM for the treatment of non-squamous NSCLC was supported by two of the phase III studies (JMEI and JMEN) (8,9). Thus, at present, CDDP plus ...

Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study

“…Furthermore, there was no treatment-related death in this study. The low frequencies of severe toxicities observed in this study are consistent with those observed in other studies [ 7 , 11 ]. Serious adverse events such as pulmonary embolism (1.6%) and pneumonia (5.6%) occurred during maintenance therapy with pemetrexed and bevacizumab in the AVAPERL study, in which the bevacizumab dose was 7.5 mg/kg [ 7 ].…”

“…Serious adverse events such as pulmonary embolism (1.6%) and pneumonia (5.6%) occurred during maintenance therapy with pemetrexed and bevacizumab in the AVAPERL study, in which the bevacizumab dose was 7.5 mg/kg [ 7 ]. A retrospective study evaluating the feasibility of cisplatin, pemetrexed, and bevacizumab (15 mg/kg) in patients with advanced nonsquamous NSCLC reported low frequencies of grade 3/4 non-hematologic toxicities (hypertension, 13%; pulmonary thromboembolism, 3%; fatigue, 3%; anorexia, 6%; gastric ulcer, 3%; and colitis, 3%) and no treatment-related deaths [ 11 ]. To the best of our knowledge, this is the first prospective study evaluating 15 mg/kg of bevacizumab in combination with standard dose cisplatin and pemetrexed for patients with nonsquamous NSCLC; our results suggest that the dose of 15 mg/kg bevacizumab and combination therapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance therapy with pemetrexed and bevacizumab is a safe and feasible regimen.…”

Bevacizumab plus cisplatin/pemetrexed then bevacizumab alone for unresectable malignant pleural mesothelioma: A Japanese safety study

“…The toxicity profile of bevacizumab plus cisplatin/pemetrexed was also similar to that reported in Japanese patients with NSCLC 24 and with advanced cervical cancer 25 . Although it is difficult to make cross‐trial comparisons due to differences in study designs, methods of assessment and patient populations, our safety data appear to be consistent with previous reports on bevacizumab‐based therapy for MPM, and did not identify any previously unknown toxicities 21,22 …”

Efficacy of cisplatin/pemetrexed with bevacizumab to treat advanced lung adenocarcinoma with different drive genes: case report and literature review

“…However, the study was not from the People’s Republic of China, and the study did not carry out subgroup analysis according to different gene mutation types. Hirai et al 25 also retrospectively evaluated the feasibility of cisplatin/pemetrexed/bevacizumab therapy as a first-line chemotherapeutic strategy for patients with advanced nonsquamous NSCLC and clarified the effectiveness and tolerability of cisplatin/pemetrexed/bevacizumab therapy in patients with nonsquamous NSCLC. However, the study was also not from the People’s Republic of China, and the dose of bevacizumab was 15 mg/kg in this study.…”