Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial

Georgoulias, Vassilis; Papadakis, E.; Alexopoulos, Athanasios; Tsiafaki, Xanthi; Rapti, Ageliki; Veslemes, M.; Palamidas, Ph.; Vlachonikolis, Ioannis G.

doi:10.1016/s0140-6736(00)04644-4

Cited by 326 publications

(204 citation statements)

References 16 publications

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“…Other trials showed similar response rates and survival, and less toxicity in patients treated with nonplatinum-based schedules compared to platinum-containing combinations (Gatzemeier et al, 1991;Gridelli et al, 1996;Georgoulias et al, 2001;Sculier et al, 2002). A recently published study compared four platinum-based regimens for advanced NSCLC (cisplatin with either paclitaxel, gemcitabine, or docetaxel, and carboplatin with paclitaxel), and showed no difference in survival (the median survival was 7.9 months for all patients) and response rate (19% for all patients).…”

Section: Discussionmentioning

confidence: 95%

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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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Section: Discussionmentioning

confidence: 95%

“…Phase III studies have reported similar response rates and overall survival in cisplatin and noncisplatin-based regimens. However, in the majority of these trials the nonplatinum regimens had a more favourable toxicity profile (Gatzemeier et al, 1991;Gridelli et al, 1996;Georgoulias et al, 2001;Kosmidis et al, 2002;Sculier et al, 2002).…”

mentioning

confidence: 99%

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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“…[12][13][14] Therapeutic regimens using docetaxel in combination with the nucleoside analogue gemcitabine, and permetrexed in combination with cisplatin, have a higher response rate in patients with adenocarcinoma differentiation compared to other histological types of lung carcinoma. 15,16 The recombinant antibody bevacizumab, targeting the VEGF protein, has been shown to be effective when used in combination with standard first-line chemotherapy; however in patients with squamous cell carcinomas, in particular the cavitating variant, it is associated with fatal pulmonary hemorrhage. It has thus been recommended for use only in lung carcinoma patients with non-squamous cell histology.…”

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confidence: 99%

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Ring¹,

Seitz

Beck

et al. 2009

Modern Pathology

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Malignant epithelial lung carcinoma can be subclassified by histology into several tumor types, including adenocarcinoma and squamous cell carcinoma. The need for a uniform method of classifying lung carcinomas is growing as clinical trials reveal treatment and side effect differences associated with histological subtypes. Diagnosis is primarily performed by morphological assessment. However, the increased use of needle biopsy has diminished the amount of tissue available for interpretation. These changes in how lung carcinomas are diagnosed and treated suggest that the development of improved molecular-based classification tools could improve patient management. We used a 551-patient surgical specimen lung carcinoma retrospective cohort from a regional hospital to assess the association of a large number of proteins with histological type by immunohistochemistry. Five of these antibodies, targeting the proteins TRIM29, CEACAM5, SLC7A5, MUC1, and CK5/6, were combined into one test using a weighted algorithm trained to discriminate adenocarcinoma from squamous cell carcinoma. Antibody-based classification on 600 lM tissue array cores with the fiveantibody test was compared to standard histological evaluation on surgical specimens in three independent lung carcinoma cohorts (combined population of 1111 patients). In addition, the five-antibody test was tested against the two-marker panel thyroid transcription factor-1 (TTF-1) and TP63. Both the five-antibody test and TTF-1/TP63 panel had similarly low misclassification rates on the validation cohorts compared to morphological-based diagnosis (4.1 vs 3.5%). However the percentage of patients remaining unclassifiable by TTF-1/TP63 (22%, 95% CI: 20-25%) was twice that of the five-antibody test (11%, 95% CI: 8-13%). The results of this study suggest the five-antibody test may have an immediate function in the clinic for helping pathologists distinguish lung carcinoma histological types. The results also suggest that if validated in prospectively defined clinical trials this classifier might identify candidates for targeted therapy that are overlooked with current diagnostic approaches.

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“…Moreover, the toxicity profile of cisplatin can influence the patients' quality of life. Several randomised phase III studies have demonstrated that nonplatinum-containing regimens have substantial efficacy against advanced/metastatic NSCLC with a more favourable toxicity profile than the corresponding cisplatin-based regimens (Douillard et al, 2001;Georgoulias et al, 2001Georgoulias et al, , 2005Kosmidis et al, 2002).…”

mentioning

confidence: 99%

“…In a randomised multicentre trial comparing docetaxel/cisplatin and docetaxel/gemcitabine as front-line chemotherapy in NSCLC patients, a significantly higher objective response rate was achieved with docetaxel/gemcitabine in adenocarcinoma than in nonadenocarcinoma patients (Georgoulias et al, 2001). To further investigate this issue, we have carried out a multicentre phase II study to evaluate the impact of RRM1 and RRM2 mRNA expression in the tumours of lung adenocarcinoma patients treated with docetaxel/gemcitabine.…”

mentioning

confidence: 99%

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

et al. 2008

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Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2 0 ,2 0 -difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (Po 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P ¼ 0.044) and overall survival (P ¼ 0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P ¼ 0.049), time to progression (9.9 vs 2.3 months; P ¼ 0.003) and overall survival (15.4 vs 3.6; P ¼ 0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy.

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Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial

Cited by 326 publications

References 16 publications

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

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

A novel five-antibody immunohistochemical test for subclassification of lung carcinoma

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

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