Phase III Trial of  Gemcitabine Plus Cisplatin  Versus Cisplatin Alone in Patients With Locally Advanced or Metastatic  Non–Small-Cell Lung  Cancer

Sandler, Alan; Nemunaitis, John; Denham, Claude; Pawel, Joachim von; Cormier, Yvon; Gatzemeier, U.; Mattson, K.; Manegold, C.; Palmer, Martin; Gregor, Anne; Nguyen, Binh Thanh; Niyikiza, Clet; Einhorn, L. H.

doi:10.1200/jco.2000.18.1.122

Cited by 652 publications

(312 citation statements)

References 15 publications

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“…Good median and 1-year survival have been consistently observed (Abratt et al, 1997;Crino et al, 1997;Einhorn, 1997;Shepherd et al, 1997). Three randomized phase III studies demonstrated the superiority of GC over other chemotherapy regimens (Cardenal et al, 1999;Crino et al, 1999;Sandler et al, 2000). It is likely that GC as an induction treatment may further improve survival in LAD-NSCLC patients.…”

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confidence: 97%

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

et al. 2002

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The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m 72 , days 1, 8, 15) and cisplatin (90 mg m 72 , day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

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confidence: 97%

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

et al. 2002

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“…This combination has shown significant activity in a number of tumour types and has become a standard regime in advanced lung cancer (Rinaldi et al, 2000;Sandler et al, 2000). However, increased toxicities resulted from combining gemcitabine with CDDP or carboplatin have been reported (Rinaldi et al, 2000;Sandler et al, 2000;Thomas et al, 2002).…”

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confidence: 99%

Preclinical relevance of dosing time for the therapeutic index of gemcitabine–cisplatin

Tanaka

Sun

et al. 2005

Br J Cancer

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The relevance of gemcitabine timing for chronotherapeutic optimisation was investigated. Healthy mice received multiple doses of gemcitabine (120, 160 or 200 mg kg À1 injection (inj) À1 ) at one of six circadian times (3, 7, 11, 15, 19 or 23 h after light onset -HALO) on days 1, 4, 7 and 10 or a single dose of gemcitabine (400 mg kg À1 ) at 11 or 23 HALO7cisplatin (5 mg kg À1 at 1 min, 4 or 8 h later). Mice bearing Glasgow osteosarcoma received multiple doses of gemcitabine (200 mg kg À1 inj À1 ) at 11 or 23 HALO7cisplatin (5 mg kg À1 inj À1 at 1 min or 4 h later) on days of 10, 13, 16 and 19 following tumour inoculation. A circadian rhythm in body weight loss was statistically validated, with 1030 HALO corresponding to the least toxic time (95% CL, 0800 to 1300). Gemcitabine dosing produced least body weight loss and least neutropenia after injection at 11 vs 23 HALO, whether the drug was given alone or with cisplatin (P ¼ 0.001). Gemcitabine -cisplatin tolerability was improved by dosing gemcitabine at 11 HALO and CDDP at 15 HALO (Po0.001). The administration of this schedule to tumour-bearing mice increased median survival three-fold as compared to treatments where both drugs were given simultaneously at 11 or 23 HALO (P ¼ 0.02). The optimal schedule would correspond to the delivery of gemcitabine upon awakening and cisplatin near mid-activity in cancer patients.

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“…Phase II studies showed response rates between 18 -26% and a mild toxicity profile (Anderson et al, 1994;Gatzemeier et al, 1996;Halme et al, 1997;Yokoyama et al, 1997;Perng et al, 1997;Takada et al, 1998;Zatloukal et al, 1998;Ten Bokkel Huinink et al, 1999). The combination of cisplatin and gemcitabine in NSCLC has been evaluated in phase III trials, reporting response rates of 22 -41% and median survival between 8.1 and 9.7 months (Cardenal et al, 1999;Crino et al, 1999;Comella et al, 2000;Sandler et al, 2000;Schiller et al, 2002).…”

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First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

Wachters¹,

Putten²,

Kramer³

et al. 2003

Br J Cancer

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The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin -gemcitabine (CG) or epirubicin -gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n ¼ 240) were randomised to receive gemcitabine 1125 mg m À2 (days 1 and 8) plus either cisplatin 80 mg m À2 (day 2) or epirubicin 100 mg m À2 (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status p2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm.

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Phase III Trial of Gemcitabine Plus Cisplatin Versus Cisplatin Alone in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

Abstract: For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.

Cited by 652 publications

References 15 publications

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

Preclinical relevance of dosing time for the therapeutic index of gemcitabine–cisplatin

First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

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