Oxaliplatin plus irinotecan and leucovorin-modulated5-fluorouracil triplet regimen every other week:a dose-finding study in patients with advanced gastrointestinal malignancies

Comella, Pasquale; Casaretti, Rossana; Rosa, Vincenzo De; Avallone, Antonio; Izzo, Francesco; Fiore, Francesco; Lapenta, Liliana; Comella, G.

doi:10.1093/annonc/mdf307

Cited by 22 publications

(22 citation statements)

References 28 publications

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“…More recently, a triplet combination of 5-FU, L-OHP and CPT-11 has emerged as a feasible and highly active regimen for mCRC patients. We (Calvo et al, 2002a, b) and others (Comella et al, 2002;Falcone et al, 2002) had previously reported a consistently high response rate and prolonged survival times with varying doses and schedules of this triplet regimen.…”

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confidence: 64%

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

Zárate¹,

Rodríguez

Bandrés³

et al. 2010

Br J Cancer

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BACKGROUND: A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome. METHODS: Eighty-seven chemotherapy-naïve mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m -2 ) and CPT-11 (150 mg m -2 ), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m -2 bid on days 1 -7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS. RESULTS: The capecitabine RD was 1000 mg m À2 bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6 -13.4) and 27 months (95% CI; 17.2 -36.8), respectively. The GSTP1-G genotype, the Kö hne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P ¼ 0.004). CONCLUSION: First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A4G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy.

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confidence: 64%

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

Zárate¹,

Rodríguez

Bandrés³

et al. 2010

Br J Cancer

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“…Measurement of disease lesions with CT or MRI scans was repeated after every four cycles, and response was classiWed according to WHO criteria [27]. Responses were conWrmed after a minimum of 4 weeks from initial documentation.…”

Section: Assessment Of Activitymentioning

confidence: 99%

“…We have already assessed this triplet in pre-treated patients with metastatic gastrointestinal carcinomas [27,28]. Here we report on the safety and activity of this regimen in untreated gastric cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group

Comella

Lorusso²,

Maiorino

et al. 2009

Cancer Chemother Pharmacol

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Purpose This phase II trial assessed the tolerability and eYcacy of a triplet of oxaliplatin, irinotecan, and Xuorouracil/folinic acid in advanced gastric cancer. Methods Patients with unresectable or metastatic gastric cancer, unexposed to palliative chemotherapy, received oxaliplatin 85 mg/m 2 iv and irinotecan 150 mg/m 2 iv on day 1, 6S-folinic acid 250 mg/m 2 iv and Xuorouracil 750 mg/m 2 iv on day 2, every 2 weeks. Response rate (RR) was assessed after a minimum of four cycles, and treatment continued up to 12 cycles. Results Sixty-three patients were treated, with a median of eight (range 1-12) cycles/patient. Two complete and 19 partial responses were registered (RR 33% [95% CI, 22-46%]). Median progression-free survival was 7.5 (95% CI, 5.6-9.4) months, and median overall survival was 12.1 (95% CI, 10.8-13.4) months. Most common grade ¸3 toxicities were neutropenia (59%), febrile neutropenia (7%), vomiting (20%), and diarrhoea (10%). All-grade neurotoxicity aVected 33% of patients. Conclusions Oxaliplatin, irinotecan, and Xuorouracil/folinic acid administered every 2 weeks are safe and active in advanced gastric cancer. Keywords

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“…This observation represented the rationale for assessing triplet regimens in front-line. Indeed, several investigators have demonstrated the feasibility and activity of different triplet combinations in phase I-II studies [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…In a previous phase I study, we have already identified the recommended doses of OXA plus IRI delivered on day 1, and levo-folinic acid (LFA)-modulated bolus 5FU on day 2, for a biweekly combination regimen [13]. This schedule of administration was selected on the ground of some in-vitro experiments on the HT29 human colon cancer cell line, demonstrating a better growth-inhibitory effect when OXA shortly preceded the exposure to SN-38 (the active metabolite of IRI) [14].…”

Section: Introductionmentioning

confidence: 99%

Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer

Comella¹,

Massidda

Palmeri

et al. 2006

Anti-Cancer Drugs

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a Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/ or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatment, 19 patients were considered as chemo-resistant and 14 patients as chemo-refractory. OXA 110 mg/m 2 (over 2 h) and IRI 175 mg/m 2 (over 1 h) were delivered on day 1,

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Oxaliplatin plus irinotecan and leucovorin-modulated5-fluorouracil triplet regimen every other week:a dose-finding study in patients with advanced gastrointestinal malignancies

Cited by 22 publications

References 28 publications

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group

Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer

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