Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study

Pozzo, Carmelo; Barone, Carlo; Szántó, J.; Pádi, Éva; Peschel, Christian; Bükki, Johannes; Gorbunova, Vera; Valvere, Vahur; Załuski, J.; Biakhov, M.; Zuber, Emmanuel; Jacques, Christian; Bugat, R.

doi:10.1093/annonc/mdh473

Cited by 159 publications

(116 citation statements)

References 24 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…The same can be said of the progression-free survival period in the ILF group of 4.5 months, which compared well with the 4.1 and 5.2 months reported recently for docetaxel-based regimens (Lee et al, 2004;Park et al, 2004). In other randomised phase II studies, continuous 5-FU/LV infusion plus irinotecan has also provided promising efficacy (ORRs of 40 -42%, median progression-free survival periods of 6.5 -6.9 months and median overall survival periods of 10.7 -11.3 months; Bouche et al, 2004;Pozzo et al, 2004). Consequently, large phase III studies are being considered to investigate irinotecan in combination with continuous 5-FU/LV infusion regimens.…”

Section: Discussionsupporting

confidence: 72%

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

Moehler¹,

Eimermacher²,

Siebler³

et al. 2005

Br J Cancer

View full text Add to dashboard Cite

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m À2 , LV 500 mg m À2 , 24-h 5-FU 2000 mg m À2 , and ELF comprised three once-daily doses of etoposide 120 mg m À2 , LV 300 mg m À2 , 5-FU 500 mg m À2 . In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29 -1.13, P ¼ 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33 -0.97; P ¼ 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P ¼ 0.4542), and overall survival was 10.8 vs 8.3 months (P ¼ 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

show abstract

Section: Discussionsupporting

confidence: 72%

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

Moehler¹,

Eimermacher²,

Siebler³

et al. 2005

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Our results demonstrate that doseintensified biweekly capecitabine and irinotecan are active against advanced gastric cancer with a 43% overall response rate (95% CI: 30.2 -56.9%) and a median response duration of 6 months. Moreover, the results achieved in this study could be favourably comparable with those of other studies that used an irinotecanbased combination regimen (Pozzo et al, 2004;Baek et al, 2006). Biweekly irinotecan and capecitabine (180 mg m À2 , day 1 and 2000 mg m À2 , days 1 -9, respectively) have also been studied against gastroesophageal cancer (Burge et al, 2006), and an overall response rate of 32% was obtained.…”

Section: Toxicitysupporting

confidence: 81%

“…Pozzo et al (2004) compared irinotecan/cisplatin and irinotecan/5-FU/leucovorin with the aim of selecting a better regimen for a comparative phase III study with cisplatin/5-FU for the treatment of advanced gastric cancer, and the overall response rate of the irinotecan/5-FU/leucovorin arm (42%) was found to be superior to that of the irinotecan/cisplatin arm (32%). In the present study, we used capecitabine instead of 5-FU and leucovorin.…”

Section: Toxicitymentioning

confidence: 99%

“…Current response rates to chemotherapy among advanced gastric cancer patients are between 10 and 20% for a single agent and between 30 and 50% for combination chemotherapy (Barone et al, 1998;Ajani et al, 2005;Moehler et al, 2005;Ohtsu et al, 2006;Nardi et al, 2007). However, during recent years, several new agents, for example, taxane, irinotecan and oxaliplatin, have been introduced for the treatment of gastric cancer (Louvet et al, 2002;Pozzo et al, 2004;Roth et al, 2004), and these drugs have shown promising response rates without sacrificing acceptable toxicity. Irinotecan (Camptor s ; Pfizer) is a semisynthetic plant alkaloid camptothecin, which inhibits DNA topoisomerase-I.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer

Sur

Sung

et al. 2007

Br J Cancer

View full text Add to dashboard Cite

Capecitabine, a prodrug of 5-FU, has been reported to generate maximal tumour activity at tumour sites and/or to improve drug tolerability as compared with 5-FU infusion, and it has also been demonstrated to act synergistically with irinotecan against some solid cancers. A previous study concluded that dose-intensified biweekly capecitabine seems to be more effective at increasing both response rate and progression-free survival time than conventional dose and schedule of capecitabine in colon cancer. We conducted this study to ascertain the efficacy and toxicity of dose-intensified biweekly capecitabine and irinotecan combination chemotherapy in chemotherapy-naïve advanced or metastatic gastric cancer patients. Patients were treated with irinotecan 130 mg m À2 intravenously for 90 min on days 1 and 15. Capecitabine at 3500 mg m À2 day À1 , divided into two sessions per day, was administered for seven consecutive days from days 1 and 15, and followed by a 7-day drug-free period, respectively. Fifty-five eligible patients were enrolled in this study from November 2003 to April 2006. There were 22 women and 33 men: median patient age was 54 years (range: 27 -81). A total of 200 treatment cycles were administered at a median number of four per patient (range: 1 -9). Intent-to-treatment analysis showed that one patient achieved complete response (1.8%), 23 partial response (41.8%), 15 stable disease (27.3%), 10 progressive disease (18.2%) and 6 were non-evaluable (10.9%). The overall response rate was 43.6% (95% confidence interval: 30.2 -56.9). The common grade 3 -4 toxicities were neutropenia in 12 (21.8%), nausea/vomiting in 3 (5.4%) and diarrhea in 4 (7.2%) patients. Median time to progression was 5 months (range: 0.5 -11 months), median survival duration was 11 months (range: 0.5 -45 months) and median response duration was 6 months (range: 0.5 -9 months). Biweekly dose-intensified capecitabine and irinotecan combination chemotherapy was active for the treatment of advanced or metastatic gastric cancers with a tolerable safety profile.

show abstract

“…Irinotecan is also well tolerated, as demonstrated by the excellent relative dose intensity. Based on these promising results, randomised phase II and III trials of combination regimens including irinotecan are ongoing (Pozzo et al, 2001) and will help to define the role of this drug further in the treatment of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial

et al. 2003

View full text Add to dashboard Cite

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m À2 every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4 -36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3 -4.4%). The median overall survival was 7.1 months (95% CI: 5.2 -9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1 -14), and the relative dose intensity was 0.98. The most common grade 3 -4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.

show abstract

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study

Abstract: Both combinations were active, with acceptable safety profiles. Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer.

Cited by 159 publications

References 24 publications

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

A phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer

Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial

Contact Info

Product

Resources

About