The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma

Abstract

BACKGROUNDGemcitabine and vinorelbine are two of the most active third‐generation agents for the treatment of advanced nonsmall cell lung carcinoma (NSCLC). The authors conducted a formal Phase II trial to evaluate the efficacy of this combination in both untreated and previously treated patients with Stage IIIB (with pleural effusion) or Stage IV NSCLC.METHODSA total of 78 patients were treated on the current Phase II trial of front‐line or second/third‐line therapy with gemcitabine and vinorelbine in NSCLC. Eligible patients manifested either untreated disease (n = 42) or had received at least one but not more than two prior chemotherapy regimens (n = 36). The median age was 59 years (range, 33–79) with 57 men (73%) and 21 women (27%). The median performance status was one (range, one to two). The initial eight patients (four untreated and four previously treated) were treated at a previously established maximum tolerated dose of vinorelbine (30 mg/m2) and gemcitabine (1000 mg/m2) on Days 1, 8, and 15, with significant myelosuppression seen in five out of eight patients requiring dose omission in the first cycle. The next 70 patients received a reduced dose of vinorelbine (25 mg/m2) followed by gemcitabine (900 mg/m2) on Days 1, 8, and 15.RESULTSSeventy eight patients were treated. Fifteen (36%) of the 42 evaluable patients who received front‐line therapy had objective responses and 14 (33%) had stable disease. In the patients with prior treatment, 6 (17%) of 36 patients had partial response and 18 patients (50%) had stable disease. Median survival time for the previously untreated patient group was 10.1 months, with a one year survival of 43% and a two year survival rate of 32%. For the previously treated patients, the median survival time was 8.5 months, with a one year survival rate of 30%. Toxic effects were notable for significant myelosuppression, with ≥Grade 3 granulocytopenia seen in 55% of the patients on the untreated arm and 67% of the patients on the previously untreated arm. Additionally, 9.5% and 13.9% (untreated and previously treated), respectively, of these patients experienced Grades 3 and 4 thrombocytopenia at some point in their treatment. A full dose delivery analysis showed that this myelosuppression resulted in Course 1, Day 15 skipped doses (even at the reduced dose level) in 42% of previously untreated patients and 47% of pretreated patients. Other side effects seen at Grades 3 and 4 in previously untreated and treated patients included anemia (9.5% and 2.8%), asthenia (4.8% and 5.5%), infection (14.3% and 5.6%), pain (9.5% and 19.4%), and pulmonary complications (4.8% and 13.8%).CONCLUSIONSGemcitabine/vinorelbine is an active, well‐tolerated combination in both front‐line and second/third‐line therapy for Stage IIIB/IV NSCLC. The response rate, median survival rate, and one year survival rate compare favorably with platinum‐based regimens. The toxicity profile of the gemcitabine/vinorelbine combination was quite favorable, with minimal Grade 3 and 4 toxic effects aside from granulocytopenia, which resulted in numerous Day 15 skipped doses but no significant febrile neutropenia or infection. The combination of gemcitabine and vinorelbine could be a useful regimen in standard clinical practice and has the potential for efficient combination with biologic/targeted therapy. Multiple randomized trials of this combination versus platinum combinations are now ongoing. Cancer 2002;95:340–353. © 2002 American Cancer Society.DOI 10.1002/cncr.10629

Phase II Study of Pemetrexed-Gemcitabine Combination in Patients with Advanced-Stage Non-Small Cell Lung Cancer

“…The combination of gemcitabine and vinorelbine has been investigated in previously treated and untreated patients with stage IIIb and IV disease (40). In the untreated group, 16 of 42 patients (36%) experienced a partial response, median overall survival was 10.1 months, and 1-and 2-year survival was 42.9% and 31.6%.…”

Gemcitabine Plus Vinorelbine as the Second-Line Treatment and Beyond in Elderly Patients with Platinum-Pretreated Advanced Non-Small Cell Lung Cancer

“…There are several reports of a salvage GV regimen in relatively younger patients (median age at each study 55-66 years) [15,16,17,21,22]. Most of these studies reported a favorable response rate (17.0-31.3%) and prolonged OS (6.5-8.5 months) [15,16,17].…”

“…Most of these studies reported a favorable response rate (17.0-31.3%) and prolonged OS (6.5-8.5 months) [15,16,17]. However, some studies which used a lower dose (gemcitabine 800 mg/m 2 ) than that of our study (1,000 mg/m 2 ) [22] and a biweekly schedule [21] as salvage therapy showed a disappointing response rate of 0-6.25%.…”

“…Also, there have been trials for frontline gemcitabine and vinorelbine (GV) combination chemotherapy in elderly patients [13,14]. Given a good safety profile and a high activity as the frontline treatment of advanced NSCLC, GV combination regimens as salvage chemotherapy have been evaluated [15,16,17]. However, most previous studies on salvage GV regimens had enrolled younger patients.…”

Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics

“…3 DOC is considered to be one of the most important anticancer drugs for clinical use. It acts by inhibiting the microtubular network that is essential for mitotic and interphase cellular functions.…”