Biweekly Chemotherapy With Oxaliplatin, Irinotecan, Infusional Fluorouracil, and Leucovorin: A Pilot Study in Patients With Metastatic Colorectal Cancer

Falcone, Alfredo; Masi, Gianluca; Allegrini, Giacomo; Danesi, Romano; Pfanner, E.; Brunetti, I.; Paolo, Antonello Di; Cupini, Samanta; Tacca, M. Del; Conte, Pierfranco

doi:10.1200/jco.2002.12.075

Cited by 152 publications

(120 citation statements)

References 32 publications

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“…Souglakos et al (2006) reported a 57% response rate when irinotecan and oxaliplatin were given 'up front' with 5-FU to a cohort of 57 patients. Falcone et al (2002) reported a higher response rate (71%) using a similar combination, as well as a 26.5-month overall survival and a 10.4-month PFS, which was comparable with the 8.8 months observed in our study. To our knowledge, there are no published studies combining irinotecan and oxaliplatin concurrently with the other major oral fluoropyrimidine, capecitabine, as a first-line treatment.…”

Section: Discussionsupporting

confidence: 90%

“…One way forward, therefore, might be to combine a fluoropyrimidine with both oxaliplatin and irinotecan in the first-line setting so that a patient receives all three drugs 'up front'. Previous studies of irinotecan and oxaliplatin with 5-FU have reported high response rates and impressive survival times (Falcone et al, 2002;Souglakos et al, 2006), suggesting that further investigation of concurrent administration of all three drugs is warranted in the first-line management of patients with metastatic colorectal cancer.…”

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confidence: 99%

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Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

et al. 2007

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The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24 -79) years, World Health Organisation performance status 0 -2 and median four marker lesions, received irinotecan 180 mg m À2 on day 1, oxaliplatin 85 -100 mg m À2 on day 15 and UFT 200 -300 mg m À2 day À1 with LV 90 mg day À1 , days 1 -21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 300 mg m À2 day À1 ), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 250 mg m À2 day À1 ). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m À2 on day 1, oxaliplatin 100 mg m À2 on day 15 and UFT 250 mg m À2 day À1 with LV 90 mg day À1 on days 1 -21 of a 28-day cycle for future studies.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

et al. 2007

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“…Eighty-four out of 124 patients (67.7%) received OHP as a first-line treatment. Fifty-five patients (44.3%) were treated with a FOLFOX-4 regimen De Gramont et al, 2000), 34 patients (27.4%) with FOLFOX-3 regimen , 30 patients (24.1%) with the association of OHP/CPT-11/c.i.5-FU/FA regimen (Falcone et al, 2002), three patients (2.4%) with OHP alone (Diaz-Rubio et al, 1998) and two patients (1.6%) with OHP/ Raltitrexed regimen (Seitz et al, 1999). All patients received a standard antiemetic treatment with ondansetron 8 mg by a i.v.…”

Section: Methodsmentioning

confidence: 99%

Hypersensitivity reactions related to oxaliplatin (OHP)

et al. 2003

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Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2 -17 exposures to OHP (Mean7s.e.: 9.471.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderatesevere reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated.

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“…Nevertheless, a high incidence of severe neutropenia, associated with greater use of haematopoietic growth factors, is often reported when 5-FU, L-HOP, and CPT-11 are simultaneously combined (Falcone et al, 2002;Souglakos et al, 2002). Hand -foot syndrome, which is frequently described with the use of continuous 5-FU infusions or capecitabine (Van Cutsem et al, 2000), was never observed, possibly because the profile of frequent oral UFT/ LV dosing may resemble that of a repeated mini-bolus (Ho et al, 1998) and the UFT dose (250 m À2 day À1 ) was lower than the 300 -350 mg m À2 day À1 used by other authors.…”

Section: Discussionmentioning

confidence: 99%

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer

et al. 2004

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A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT) þ leucovorin (LV) þ oxaliplatin alternated with UFT/LV þ irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2 -73.3%), and the median progressionfree survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand -foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC.

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Biweekly Chemotherapy With Oxaliplatin, Irinotecan, Infusional Fluorouracil, and Leucovorin: A Pilot Study in Patients With Metastatic Colorectal Cancer

Cited by 152 publications

References 32 publications

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

Hypersensitivity reactions related to oxaliplatin (OHP)

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer

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