Phase III Randomized Trial Comparing Three Platinum-Based Doublets in Advanced Non–Small-Cell Lung Cancer

Scagliotti, Giorgio V.; Marinis, Filippo de; Rinaldi, Massimo; Crinò, Lucio; Gridelli, Cesare; Ricci, Sergio; Matano, Elide; Boni, C.; Marangolo, M.; Failla, Giuseppe; Altavilla, Giuseppe; Adamo, Vincenzo; Ceribelli, Anna; Clerici, M.; Costanzo, F. Di; Frontini, L.; Tonato, Maurizio

doi:10.1200/jco.2002.02.068

Cited by 804 publications

(560 citation statements)

References 19 publications

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“…However, which new anti-cancer drug is better than the others is still unknown (Scagliotti et al, 2002;Schiller et al, 2002). Generally, there was no obvious survival difference when these new anticancer drugs were used in combination with cisplatin.…”

Section: Discussionmentioning

confidence: 99%

“…Generally, there was no obvious survival difference when these new anticancer drugs were used in combination with cisplatin. However, the toxicity profiles could differ among the new anticancer drugs in combination with cisplatin, due to the pre-existing different toxicity profiles of the new anticancer drugs, such as the higher incidence of peripheral neuropathy with paclitaxel vs the more myelosuppressive effect of vinorelbine (Scagliotti et al, 2002;Schiller et al, 2002). Furthermore, the performance and staging statuses of the study population predicted a major part of the treatment results: the better the performance status and staging status of the study population, the better the response rate and the survival, and also the less severe the treatment toxicities.…”

Section: Discussionmentioning

confidence: 99%

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A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

Shih

et al. 2004

Br J Cancer

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Phase II studies have suggested that weekly paclitaxel has a higher response rate and better toxicity profile than the conventional schedule of once every 3 or 4 weeks. Our aim was to evaluate the efficacy of weekly paclitaxel plus cisplatin (PC) vs vinorelbine plus cisplatin (VC) in chemonaïve non-small-cell lung cancer (NSCLC) patients. From October 2000 to May 2002, 140 patients were enrolled. The treatment dose was P 66 mg m À2 intravenous infusion (i.v.) on days 1, 8, and 15, and C 60 mg m À2 i.v. on day 15, or V 23 mg m À2 i.v. on days 1, 8, and 15, and C 60 mg m À2 i.v. on day 15, every 4 weeks. In all, 281 cycles of PC and 307 cycles of VC were given to the patients in the PC and VC arms, respectively. There were 26 partial responses and one complete response (overall 38.6%) in the PC arm, and no complete responses, but 27 partial responses (overall 38.6%) in the VC arm. Myelosuppression was more common in the VC arm (Po0.001). Peripheral neuropathy and myalgia were significantly more common in the PC arm (Po0.001). The median time to disease progression was 6 months in the PC arm and 8.4 months in the VC arm (P ¼ 0.0344). The median survival time was 11.7 months in the PC arm and 15.4 months in the VC arm (P ¼ 0.297). We concluded that weekly PC is not suggested for NSCLC patients due to the relatively shorter progression-free survival and more common nonhaematological toxicities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

Shih

et al. 2004

Br J Cancer

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“…Therefore for chronic administration, tipifarnib at 300 mg BID with × 14 days, gemcitabine 750 mg/m2 day 1, 8 and cisplatin 60 mg/m2 day 1 on a 21-day schedule was recommended instead of the MTD. Of note, these doses were also significantly lower than the standard efficacious gemcitabine and cisplatin doses in clinical use [11,12,25,38,41]. As the 21-day schedule of gemcitabine and cisplatin appears to have much less hematologic toxicity and is more tolerable; from the beginning, our study should have assessed a 21-day schedule rather than the 28-day schedule, excluded heavily pretreated patients, and explored a discontinuous dosing schedule to decrease cumulative toxicity to make this therapy more "deliver-able.…”

Section: Discussionmentioning

confidence: 97%

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors

Chow

Eckhardt

O’Bryant

et al. 2007

Cancer Chemother Pharmacol

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Purpose-This phase I study was conducted to evaluate the safety, tolerability, pharmacological properties and biological activity of the combination of the lonafarnib, a farnesylproteintransferase (FTPase) inhibitor, with gemcitabine and cisplatin in patients with advanced solid malignancies.Experimental design-This was a single institution study to determine the maximal tolerated dose (MTD) of escalating lonafarnib (75-125 mg po BID) with gemcitabine (750-1,000 mg/m 2 on days 1, 8, 15) and fixed cisplatin (75 mg/m 2 day 1) every 28 days. Due to dose-limiting toxicities (DLTs) of neutropenia and thrombocytopenia in initial patients, these patients were considered "heavily pretreated" and the protocol was amended to limit prior therapy and re-escalate lonafarnib © Springer-Verlag 2007 Correspondence to: Lia Gore, lia.gore@uchsc.edu. NIH Public Access Author ManuscriptCancer Chemother Pharmacol. Author manuscript; available in PMC 2010 January 29. in "less heavily pre-treated patients" on 28-day and 21-day schedules. Cycle 1 and 2 pharmacokinetics (PK), and farnesylation of the HDJ2 chaperone protein and FPTase activity were analyzed.Results-Twenty-two patients received 53 courses of therapy. Nausea, vomiting, and fatigue were frequent in all patients. Severe toxicities were observed in 91% of patients: neutropenia (41%), nausea (36%), thrombocytopenia (32%), anemia (23%) and vomiting (23%). Nine patients withdrew from the study due to toxicity. DLTs of neutropenia, febrile neutropenia, thrombocytopenia, and fatigue limited dose-escalation on the 28-day schedule. The MTD was established as lonafarnib 75 mg BID, gemcitabine 750 mg/m 2 days 1, 8, 15, and cisplatin 75 mg/m 2 in heavily pre-treated patients. The MTD in the less heavily pre-treated patients could not be established on the 28-day schedule as DLTs were observed at the lowest dose level, and dose escalation was not completed on the 21-day schedule due to early study termination by the Sponsor. No PK interactions were observed. FTPase inhibition was not observed at the MTD, however HDJ-2 gel shift was observed in one patient at the 100 mg BID lonafarnib dose. Anti-cancer activity was observed: four patients had stable disease lasting >2 cycles, one subject had a complete response, and another had a partial response, both with metastatic breast cancer. Conclusion-Lonafarnib

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“…In the majority of phase III studies, stage IIIB contribute 10 -40% (Frasci et al, 2000;Ranson et al, 2000;Kelly et al, 2001;Scagliotti et al, 2002;Schiller et al, 2002) of patients and stage IV patients would vary considerably in disease bulk outside the thorax (Frasci et al, 2000;Ranson et al, 2000;Scagliotti et al, 2002). Systemic therapy is associated with a median survival ranging from 6 to 8 months.…”

Section: Discussionmentioning

confidence: 99%

A phase I trial of high-dose palliative radiotherapy plus concurrent weekly Vinorelbine and Cisplatin in patients with locally advanced and metastatic NSCLC

et al. 2005

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The role of concurrent chemoradiotherapy (CRT) in patients with non-small-cell lung cancer (NSCLC) unsuitable for radical therapy but who require locoregional treatment has not been defined. The aims of this phase I trial were thus to develop a novel regimen of weekly chemotherapy concurrent with high-dose palliative RT (40 Gy/20 fractions) and assess its tolerability, objective and symptomatic response rates. Eligible patients had stage I -IIIB NSCLC unsuitable for radical RT or limited stage IV disease, ECOG PSp1 and required locoregional therapy. Treatment was RT (40 Gy/20 fractions/5 per week) and weekly Vinorelbine plus Cisplatin escalated in six planned dose levels (DLs). At 4 weeks post-RT, patients received two cycles of Cisplatin 80 mg m À2 day 1 þ Vinorelbine 25 mg m À2 days 1, 8, 15. Dose-limiting toxicities (DLTs) were defined in the CRT phase. Disease-related symptoms were assessed by the Lung Cancer Symptom Scale. In all, 24 patients accrued, stage IIIB (n ¼ 12) and IV disease (n ¼ 10). The highest administered dose was at DL 4, Vinorelbine 30 mg m À2 þ Cisplatin 20 mg m À2 with DLTs of grade 4 neutropenia in two of three patients. No grade 3 or 4 nonhaematological toxicities were observed. The overall radiological response rate was 65% (n ¼ 23: complete response 4% and partial response 61%) and infield FDG-PET responses were seen in 89% (n ¼ 18). There was an improvement or stabilisation of symptoms and quality of life. Dose level 3, Vinorelbine 25 mg m À2 þ Cisplatin 20 mg m À2 , is recommended for further assessment. This regimen was tolerable and produced meaningful responses for patients for whom locoregional control is required, but who are unsuitable for radical CRT.

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Phase III Randomized Trial Comparing Three Platinum-Based Doublets in Advanced Non–Small-Cell Lung Cancer

Abstract: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

Cited by 804 publications

References 19 publications

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors

A phase I trial of high-dose palliative radiotherapy plus concurrent weekly Vinorelbine and Cisplatin in patients with locally advanced and metastatic NSCLC

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