Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

Marinis, Filippo de; Migliorino, Maria Rita; Paoluzzi, Luca; Portalone, Luigi; Ariganello, Ottaviano; Cortesi, Enrico; Gamucci, Teresa; Gasperoni, Silvia; Cipri, Antonino; Martelli, Olga; Nelli, Fabrizio

doi:10.1016/s0169-5002(02)00500-7

Cited by 14 publications

(8 citation statements)

References 24 publications

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“…It is encouraging that the patients were older (median age, 69 vs 63 years) and included fewer females (6 vs 14 -26%) than in these other studies, and the 2-year survival rate (17.7%) and response rate (79%) were good and similar to those for irinotecan/cisplatin rather than cisplatin/etoposide. Recent large randomized trials of cisplatin/etoposide with or without newer cytotoxic agents have demonstrated a MST of 8.0 -10.6 months in previously untreated patients with ED-SCLC (De Marinis et al, 2003, Georgoulias et al, 2004Niell et al, 2005). In addition, a recent meta-analysis of randomized trials demonstrated that patients who received a regimen containing cisplatin had a significant increase in the probability of response and survival (Pujol et al, 2000;Hotta et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

et al. 2006

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To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0 -2), agep75 years, and adequate organ function. The patients' characteristics were: male/female ¼ 56/5; PS 0/1/2 ¼ 19/38/4; median age (range) ¼ 68 years(51 -75 years); limited disease (LD)/extensive disease (ED) ¼ 27/34. The patients received irinotecan (50 mg m À2 ) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72 -91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17 -41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.

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Section: Discussionmentioning

confidence: 99%

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

et al. 2006

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“…dyspnea at normal level of activity or dyspnea at rest) reported in clinical trials retrieved by electronic search. Grades III/IV pulmonary toxicity of gemcitabine are reported in a range of 0-5% for patients with various solid tumors [11][12][13] and up to 13.8% in NSCLC pretreated patients [14][15][16][17][18][19]. This grade III/IV pulmonary toxicity get sometimes worse despite treatments and patient's death are unfortunately also reported [20][21][22][23].…”

Section: Epidemiological Datamentioning

confidence: 99%

Gemcitabine‐induced severe pulmonary toxicity

Barlési

Villani

Doddoli

et al. 2004

Fundamemntal Clinical Pharma

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Gemcitabine is a relatively new deoxycytidine analog (2',2'-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.

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“…5 However, cisplatin generates low success rates and, like many conventional, nontargeted chemotherapeutics, it produces severe side effects. 6 Therefore, new treatment regimens are required to increase the efficacy of cisplatin, enhancing antitumor effects while reducing dosage and side effects.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Smac Promotes Cisplatin-Induced Apoptosis by Activating Caspase-3 and Caspase-9 in Lung Cancer A549 Cells

Qin

Yang

Wang

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Second mitochondrial-derived activator of caspase (Smac) plays crucial roles in mitochondrial apoptosis pathways and promotes chemotherapy-induced apoptosis. In this study, Smac levels were examined in various lung cancer cell lines, and the effects of overexpressed Smac in the nonsmall-cell lung cancer cell line A549 were assayed by stable transfection of Smac. Subsequently, MTT assays, cell counting, and flow cytometry were applied to show that overexpression of Smac inhibits cell viability and cell growth and enhances apoptosis after cisplatin treatment. Western blotting was performed before and after cisplatin treatment to demonstrate that drug treatment could release Smac from mitochondria into the cytosol and promote apoptosis by activating caspase-3 and caspase-9. Promotion of apoptosis by cytosolic Smac could be blocked by pretreating cells with the caspase-9 inhibitor z-LEHD-FMK. Our findings indicate that overexpressed Smac significantly inhibited A549 cell growth and promoted apoptosis following cisplatin treatment due to the release of Smac from mitochondria into the cytosol, which increased the activities of caspase-3 and caspase-9.

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Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

Cited by 14 publications

References 24 publications

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

Gemcitabine‐induced severe pulmonary toxicity

Overexpression of Smac Promotes Cisplatin-Induced Apoptosis by Activating Caspase-3 and Caspase-9 in Lung Cancer A549 Cells

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