Treatment of Non-Small Cell Lung Cancer: Focus on Pemetrexed Disodium

2010 ◽  
Vol 2 ◽  
pp. CMT.S5262
Author(s):  
Josephine Feliciano ◽  
Jyoti Patel
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Folic Acid Supplementation ◽  
Small Cell ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Line Setting

Pemetrexed (Alimta, Eli Lilly) is a multi-targeted anti-folate originally approved for its use in malignant mesothelioma. Based on results from phase III clinical investigations, it is now approved for use as a single agent in the second-line setting and in combination with platinum therapy in the first-line setting for advanced non-small cell lung cancer. It is also under investigation in earlier stages of non small cell lung cancer including in the adjuvant setting and with radiation. It has shown to be particularly efficacious for non-squamous histology and is well tolerated. Toxicity includes, but is not limited to hematologic toxicity and gastrointestinal toxicity, which are minimized by vitamin B12 and folic acid supplementation. Recent analyses also suggest cost-effectiveness of this agent in patient with advanced, non-squamous cell non-small cell lung cancer.

Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (20) ◽  
pp. 3284-3289 ◽  
Author(s):  
Jyoti D. Patel ◽  
Thomas A. Hensing ◽  
Alfred Rademaker ◽  
Eric M. Hart ◽  
Matthew G. Blum ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Time Curve ◽  
Grade 3

PurposeThis study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non–small-cell lung cancer (NSCLC).Patients and MethodsPatients received pemetrexed 500 mg/m2, carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity.ResultsFifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed ≥ six treatment cycles, and nine (18%) completed ≥ 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest—anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases.ConclusionThis regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.

Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

2007 ◽  
Vol 25 (12) ◽  
pp. 1545-1552 ◽  
Author(s):  
Ulrich Gatzemeier ◽  
Anna Pluzanska ◽  
Aleksandra Szczesna ◽  
Eckhard Kaukel ◽  
Jaromir Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Double Blind

Purpose Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL). Results A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild). Conclusion Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.

A Randomized Phase III Study of Single-Agent Amrubicin Vs. Carboplatin/Etoposide in Elderly Patients With Extensive-Disease Small-Cell Lung Cancer

2014 ◽  
Vol 15 (2) ◽  
pp. 96-102 ◽  
Author(s):  
Ikuo Sekine ◽  
Hiroaki Okamoto ◽  
Takeshi Horai ◽  
Kazuhiko Nakagawa ◽  
Hironobu Ohmatsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Phase Iii Study

Vinorelbine: A New Antineoplastic Drug for the Treatment of Non-Small-Cell Lung Cancer

1996 ◽  
Vol 30 (5) ◽  
pp. 501-506 ◽  
Author(s):  
Suzanne Fields Jones ◽  
Howard A Burris
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Vinca Alkaloid ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Ii Studies

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, and dosage and administration guidelines for vinorelbine in the treatment of non-small-cell lung cancer (NSCLC). DATA SOURCES: A MEDLINE search (1989–1995) using the terms vinorelbine and Navelbine was conducted. Additional unpublished data were provided by Glaxo Wellcome Drug Information. STUDY SELECTION AND DATA EXTRACTION: The articles chosen for inclusion all appeared in peer-reviewed journals. Pertinent abstracts, as judged by the authors, were also included. DATA SYNTHESIS: Vinorelbine is a new semisynthetic vinca alkaloid approved by the Food and Drug Administration for the first-line treatment of patients with advanced NSCLC. The drug demonstrated a broad spectrum of antitumor activity in preclinical studies and produced dose-limiting neutropenia in Phase I trials. In Phase II studies, an overall response rate of approximately 30% was reported with single-agent vinorelbine. Furthermore, in large, multicenter, randomized Phase III trials, treatment with vinorelbine alone and in combination with cisplatin resulted in improved survival compared with controls. The drug was well tolerated, with granulocytopenia being the most commonly reported adverse effect. However, the incidence of fever and hospitalization associated with this granulocytopenia was exceptionally low. The recommended dose is 30 mg/m2 weekly administered by intravenous injection or infusion. CONCLUSIONS: As no specific chemotherapy regimen has previously been regarded as standard therapy for advanced NSCLC, vinorelbine is a promising new treatment for this patient population. It has been shown in several randomized, controlled trials to increase survival without compromising quality of life.

Randomized, Double-Blind, Placebo-Controlled Phase II Study of Single-Agent Oral Talactoferrin in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer That Progressed After Chemotherapy

2011 ◽  
Vol 29 (31) ◽  
pp. 4129-4136 ◽  
Author(s):  
Purvish M. Parikh ◽  
Ashok Vaid ◽  
Suresh H. Advani ◽  
Raghunadharao Digumarti ◽  
Jayaprakash Madhavan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Patient Population ◽  
Single Agent ◽  
Locally Advanced ◽  
Anticancer Therapy ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung

Purpose To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non–small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed. Patients and Methods Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety. Results TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC. Conclusion TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.

Phase III Comparative Study of High-Dose Cisplatin Versus a Combination of Paclitaxel and Cisplatin in Patients With Advanced Non–Small-Cell Lung Cancer

2000 ◽  
Vol 18 (19) ◽  
pp. 3390-3399 ◽  
Author(s):  
Ulrich Gatzemeier ◽  
Joachim von Pawel ◽  
Maya Gottfried ◽  
G.P. M. ten Velde ◽  
Karin Mattson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Phase Iii ◽  
High Dose ◽  
Time To Progression ◽  
Small Cell Lung ◽  
Improvement In Survival

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non–small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m2) or a combination of paclitaxel (175 mg/m2, 3-hour infusion) and cisplatin (80 mg/m2) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P = .028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P = .026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P = .862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

A randomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity.

1994 ◽  
Vol 12 (7) ◽  
pp. 1427-1435 ◽  
Author(s):  
P I Clark ◽  
M L Slevin ◽  
S P Joel ◽  
R J Osborne ◽  
D I Talbot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Randomized Trial ◽  
Cell Lung Cancer ◽  
Neutrophil Count ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Small Cell ◽  
Hematologic Toxicity ◽  
Small Cell Lung

PURPOSE Etoposide is a schedule-dependent drug, as demonstrated by the superiority of 5 consecutive daily infusions over a continuous 24-hour infusion in patients with small-cell lung cancer. A randomized trial has therefore been conducted to compare an extended 8-day regimen with the 5-day schedule. PATIENTS AND METHODS Ninety-four patients with small-cell lung cancer (35 limited disease, 59 extensive disease) were randomized to receive single-agent etoposide 500 mg/m2, either as 5 daily 2-hour infusions of 100 mg/m2 or as 8 daily 75-minute infusions of 62.5 mg/m2, both repeated every 3 weeks for six cycles. Single-agent carboplatin was administered at relapse in both arms of the study. Patients were stratified at randomization according to extent of disease and Karnofsky performance status (KPS). RESULTS The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences). The time over which plasma etoposide exceeded low plasma concentrations was significantly longer in patients who responded compared with patients who did not respond. This was most significant for time at concentrations greater than 1, 1.5, and 2 micrograms/mL. Hematologic toxicity was significantly worse in the 5-day arm of the study (cycle no. 1 nadir neutrophil count, 0.8 x 10(9)/L v 1.7 x 10(9)/L). Stepwise regression analysis found duration of exposure to plasma etoposide greater than 3 micrograms/mL to be predictive of nadir neutrophil count and duration of exposure to plasma etoposide greater than 2 micrograms/mL to be predictive of nadir WBC count. CONCLUSION The 5-day and 8-day regimens had equivalent activity in small-cell lung cancer. A pharmacokinetic association between concentrations of etoposide and response and toxicity was found. Antitumor activity was associated with the maintenance of lower levels of etoposide than found to be associated with hematologic toxicity. This supports the hypothesis that the schedule of etoposide administration may affect efficacy and toxicity, and that prolonged exposure to low concentrations of etoposide may improve the therapeutic ratio for this drug.

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