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 Additional unpublished data were provided by Glaxo Wellcome Drug Information.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.

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.

scholarly journals Immunotherapy in non-metastatic non-small cell lung cancer: Can the benefits of stage IV therapy be translated into earlier stages?

2018 ◽  
Vol 10 ◽  
pp. 175883591877281 ◽  
Author(s):  
Griet Deslypere ◽  
Dorothée Gullentops ◽  
Els Wauters ◽  
Johan Vansteenkiste
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR) activating mutations or anaplastic lymphoma kinase ( ALK) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC. Aside from chemotherapy and targeted therapy, immunotherapy has become the third pillar in the treatment armamentarium of advanced NSCLC. Antigen-specific immunotherapy (cancer vaccination) has been disappointing in large phase III clinical trials in stages I–III NSCLC. Based on the recent breakthroughs with immune checkpoint inhibitor immunotherapy in metastatic NSCLC, much hope currently rests on the use of this approach in patients with stage I–III NSCLC as well. Here we give a brief overview of how most new therapeutic approaches for advanced NSCLC failed in other stages, and then elaborate on the role of immunotherapy in patients with stage I–III NSCLC.

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.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With Chemotherapy

2004 ◽  
Vol 22 (9) ◽  
pp. 1589-1597 ◽  
Author(s):  
Nasser Hanna ◽  
Frances A. Shepherd ◽  
Frank V. Fossella ◽  
Jose R. Pereira ◽  
Filippo De Marinis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Small Cell ◽  
Phase Iii ◽  
Second Line ◽  
Small Cell Lung ◽  
Previously Treated

Purpose To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non—small-cell lung cancer (NSCLC) previously treated with chemotherapy. Patients and Methods Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m2 intravenously (IV) day 1 with vitamin B12, folic acid, and dexamethasone or docetaxel 75 mg/m2 IV day 1 with dexamethasone every 21 days. The primary end point was overall survival. Results Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P = .105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P < .001), febrile neutropenia (12.7% v 1.9%; P < .001), neutropenia with infections (3.3% v 0.0%; P = .004), hospitalizations for neutropenic fever (13.4% v 1.5%; P < .001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P = .092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P < .001) and all grade alopecia (37.7% v 6.4%; P < .001) compared with patients receiving pemetrexed. Conclusion Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.

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

scholarly journals RET Inhibitors in Non-Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4415
Author(s):  
Priscilla Cascetta ◽  
Vincenzo Sforza ◽  
Anna Manzo ◽  
Guido Carillio ◽  
Giuliano Palumbo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Good Tolerability ◽  
Phase Ii Studies ◽  
Nsclc Patients

RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

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.

A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small cell lung cancer with wild type EGFR (OLCSG1202).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20614-e20614
Author(s):  
Akihiro Bessho ◽  
Nobuaki Ochi ◽  
Shoichi Kuyama ◽  
Nobukazu Fujimoto ◽  
Takahiro Umeno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Thymidine Phosphorylase ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Phase Iii ◽  
Wild Type ◽  
Small Cell Lung

e20614 Background: S-1 is an oral fluoropyrimidine anticancer agent that combines tegafur, gimeracil, and oteracil potassium. Two phase III trials in advanced non-small cell lung cancer (NSCLC) showed the non-inferiority of combination of S-1 with carboplatin or cisplatin compared with standard platinum doublet chemotherapy. Although the S-1/platinum is one of the first line combinations for advanced NSCLC, efficacy and safety of the regimen in the elderly remain unknown. Methods: Patients were required to be previously untreated advanced NSCLC with wild-type EGFR, aged 70 or more, PS of 0-2. They received oral S-1 (40 mg/m2, twice daily) for 2 weeks and carboplatin (AUC 5 on day 1) every 4 weeks as an induction treatment. After 4 cycles of the induction, S-1 alone (40 mg/m2, twice daily for 2 weeks) was administrated every 4 weeks as a maintenance therapy until PD. Primary endpoint was overall response rate (ORR), which was expected more than 20%, and secondary endpoints included disease control rate (DCR), PFS, OS, and toxicity profile. The association between clinical outcomes and gene expressions including thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase, VEGF and ERCC1 in tumors was evaluated. Results: Thirty-three patients were enrolled between March 2013 and June 2015. Median age was 78 years old (range: 70 – 89), and 51.5% had a PS of 0. ORR was 30.3% (95% CI: 14.6 – 46.0%) and DCR was 57.6% (95% CI: 40.7 – 74.4%). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%) and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. Median PFS and OS times were 134 days (95% CI: 79 – 173) and 479 days (95% CI: 250 – 571), respectively. Low thymidine phosphorylase expression was associated with DCR (P < 0.01). Conclusions: Carboplatin plus S-1 showed preferable efficacy and tolerable toxicity for elderly with NSCLC. (Clinical trial number: UMIN000009345) Clinical trial information: 9345.

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