Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines

Machover, D.; Dı́az-Rubio, Eduardo; Gramont, Aimery de; Schilf, A.; Gastiaburu, J; Brienza, S.; Itzhaki, M.; Metzger, Gérard; N'Daw, D; Vignoud, J.; Abad, Albert; François, Ετιεννε; Gamelin, Érick; Marty, M.; Sastre, Javier; Seitz, Jean‐François; Ychou, Marc

doi:10.1093/oxfordjournals.annonc.a010489

Cited by 355 publications

(140 citation statements)

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“…This kind of toxicity has been sporadically reported in clinical trials focusing on the effectiveness of OHP in chemotherapy or described as case reports (Machover et al, 1996;Diaz Rubio et al, 1998;Tournigand et al, 1998;Larzilliere et al, 1999;Medioni et al, 1999;De Gramont et al, 2000;Dold et al, 2002;Monnet et al, 2002).…”

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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“…Response rates are rarely (and then not reproducibly) above 10% with any of the new agents tested [20]. Oxaliplatin has also a relatively low activity as single agent in second line treatment [21,22], but one small phase II trial reported an unusual high response rate in second line treatment with the combination of oxaliplatinÐ5-FU/LV [23].…”

Section: Discussionmentioning

confidence: 99%

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU)

Cutsem¹,

Cunningham

Huinink

et al. 1999

European Journal of Cancer

101

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The aim of this prospective study was to assess the eYcacy, clinical bene®t and safety of in patients with stringently-de®ned 5-¯uorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m 2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18±53 +). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from ®rst administration of CPT-11 was 10.4 months or 45 weeks (range: 3±66 + weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade ! 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m 2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical bene®t. The toxicity pro®le of CPT-11 is becoming better understood and has been considerably improved. #

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“…Two phase II multicentre studies have evaluated oxaliplatin as second-line monotherapy in a total of 109 patients with histologically proven colorectal adenocarcinoma (Machover et al, 1996). All patients were resistant to 5-FU and had non-resectable metastases, but they were in good general condition.…”

Section: Second-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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Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines

Cited by 355 publications

References 6 publications

Hypersensitivity reactions related to oxaliplatin (OHP)

Hypersensitivity reactions related to oxaliplatin (OHP)

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU)

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

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