A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer

Lévi, Françis; Misset, Jean-Louis; Brienza, S.; Adam, René; Metzger, Gérard; Itzakhi, Moshe; Caussanel, J. P.; Kunstlinger, F; Lecouturier, S.; Descorps-Declère, A.; Jasmin, C; Bismuth, H; Reinberg, A

doi:10.1002/1097-0142(19920215)69:4<893::aid-cncr2820690410>3.0.co;2-x

Cited by 312 publications

(124 citation statements)

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“…When OHP is infused in a chronomodulate setting (as a 12-h infusion) or flat infusion for 5 days, these hypersensitivity reactions do not occur. In particular, 151 patients submitted to 1087 constant rate continuous infusion courses of OHP, and 491 patients submitted to 3106 chronomodulate OHP courses did not experience any hypersensitivity reactions (Caussanel et al, 1990;Levi et al, 1992Levi et al, , 1993Levi et al, , 1994bLevi et al, , 1997Levi et al, , 1999Bertheault-Cvitkovic et al, 1996). Therefore, the incapacity of these schedules to produce hypersensitivity might be due to a long time infusion rather than to failure of activation of the immune system (which presents a circadian rhythm) in a chronomodulate setting (Levi et al, 1994a).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Hypersensitivity reactions related to oxaliplatin (OHP)

et al. 2003

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“…Oxaliplatin showed additive or synergistic activity when associated to 5-FU, even in 5-FU-resistant cell lines (Becouarn et al, 2001). It has been registered worldwide for the treatment of advanced colorectal cancer, where, in association with 5-FU, it was reported to yield a response rate of 36 -58% (Levi et al, 1992;Levi et al, 1994;De Gramont et al, 2000). In in vitro studies, oxaliplatin was demonstrated to inhibit the growth of several gastric cancer cell lines (Eriguchi et al, 2003).…”

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A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

et al. 2005

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The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m À2 on day 1, FA 200 mg m À2 as a 2 h infusion followed by bolus 5-FU 400 mg m À2 and a 22 h infusion of 5-FU 600 mg m À2 , repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

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“…In studies carried out by Levi et al (1992), Bertheault-Cvitkovic et al (1996) and Giacchetti et al (1997), in which 20-30% of patients from various trials were referred for 48-h infusion, and FA (500 mg m-2), given for 2 h on each of the 2 days. All patients had at least one metastasis, and 15 had two or more.…”

Section: Combination Therapy First-line Treatmentmentioning

confidence: 99%

“…Examples of the clinical trials undertaken with oxaliplatin are outlined below (Levi et al, 1992;BertheaultCvitkovic et al, 1996;Bismuth et al, 1996;Machover et al, 1996; Becouarn et al, 1997; Giacchetti et al, 1997 The results of this study are shown in Table 1. A partial response was achieved in 10 of the 37 evaluable patients, giving an overall response rate of 27%, which is in line with the rate expected for 5-FU/leucovorin as first-line treatment.…”

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Oxaliplatin (L-OHP): a new reality in colorectal cancer

Bleiberg

1998

Br J Cancer

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Summary Oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP) is a new platinum derivative for the treatment of advanced colorectal cancer. Preclinical data have shown that oxaliplatin is active in a wide range of human and murine tumour cell lines, and has been found to be non-cross-resistant with cisplatin in various cisplatin-resistant cell lines and tumours. Oxaliplatin in combination with 5-fluorouracil (5-FU) leads to synergistic antiproliferative activity both in vivo and in vitro. Clinical data have shown that oxaliplatin is active and well tolerated both as monotherapy and in combination with 5-FU/folinic acid in first-or second-line treatment of patients with metastatic colorectal cancer. Oxaliplatin has a very good safety profile, and studies have confirmed that peripheral sensory neuropathy is related to the cumulative dose of oxaliplatin administered and that this neuropathy is generally reversible after discontinuation of treatment. High response rates and prolonged survival have been achieved in metastatic colorectal cancer patients, even after 5-FU failure.Keywords: advanced colorectal cancer; first-line treatment; 5-fluorouracil/folinic acid; oxaliplatin; second-line treatment; synergistic antiproliferative activity Oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP) is a new platinum derivative in which oxalate is the hydrolysable ligand and diaminocyclohexane (DACH) the carrier ( Figure 1). The drug is the first clinically available platinum derivative that has been approved in France for the treatment of advanced colorectal cancer.Preclinical data have shown that oxaliplatin is active in a wide range of human and murine tumour cell lines (Silvestro et al, 1990). The National Cancer Institute's Anticancer Drug Screening Programme has shown oxaliplatin to have a very different profile from that of cisplatin when tested on colon cell lines with no crossresistance with cisplatin in most cell lines (Rixe et al, 1996). DNA adducts of oxaliplatin are not recognized by the DNA mismatch repair proteins. The combination of oxaliplatin with other drugs, such as 5-fluorouracil (5-FU) and CPT-I 1, can lead to synergistic antiproliferative activity in vivo and in vitro (Raymond et al, 1996.Five phase I studies have been carried out, involving 122 patients (Mathe et al, 1986;Caussanel et al, 1990;Extra et al, 1990). From these studies, it was clear that haematological toxicity was minimal, with no nephrotoxicity, ototoxicity or alopecia; the doselimiting toxicity was a peripheral sensory neuropathy that was related to the cumulative dose of oxaliplatin administered, and was generally reversible after treatment discontinuation. However, the toxicity profile of oxaliplatin will be discussed in more detail in the following paper. The maximal tolerated dose was 200 mg m-2, and the recommended dose for treating these patients in phase II studies was 130 mg m-2 every 3 weeks.Clinical data have shown that oxaliplatin is active and well tolerated, both as monotherapy and in combination with 5-...

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A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer

Cited by 312 publications

References 22 publications

Hypersensitivity reactions related to oxaliplatin (OHP)

Hypersensitivity reactions related to oxaliplatin (OHP)

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

Oxaliplatin (L-OHP): a new reality in colorectal cancer

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