BIOMAT Database Logo BIOMAT Database Logo

Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate. 1990

J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Unité de Recherche Associée, Centre National de la Recherche Scientifique, Paris, France.

The toxic effects and tissue uptake of both cisplatin and oxaliplatin--[(1R, 2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O']platinum--were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II-IV and the incidence of distal paresthesias were 10 or more times higher (P less than .05) with schedule A than with schedule B. In addition, vomiting was 55% higher (P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin (P less than .001) and its maximum tolerated dose (P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m2, delivered according to the circadian rhythm-modulated rate.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009944 Organoplatinum Compounds Organic compounds which contain platinum as an integral part of the molecule. Compounds, Organoplatinum
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D005260 Female Females

Related Publications

J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
A phase I study of 5-day continuous venous infusion of carboplatin at circadian rhythm-modulated rate compared with constant rate.
January 1996, Anticancer research,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate.
January 1993, European journal of cancer (Oxford, England : 1990),
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
A phase I trial of 21-day continuous venous infusion of alpha-interferon at circadian rhythm modulated rate in cancer patients.
December 1991, Journal of immunotherapy : official journal of the Society for Biological Therapy,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
A phase I study of recombinant interferon-alpha administered as a seven-day continuous venous infusion at circadian-rhythm modulated rate in patients with cancer.
February 1995, American journal of clinical oncology,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients.
March 1988, Cancer research,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Phase I trial of homoharringtonine administered as a 5-day continuous infusion.
January 1983, Cancer treatment reports,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Phase I-II trial of a 5-day continuous infusion of vinblastine sulfate.
January 1984, Anticancer research,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Phase I trial of 5-day continuous infusion aziridinylbenzoquinone (AZQ, diazaquone, NSC 182968).
February 1986, American journal of clinical oncology,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
A phase I trial of 5-day continuous infusion cisplatin and interferon alpha.
January 1995, Cancer chemotherapy and pharmacology,
J P Caussanel, and F Lévi, and S Brienza, and J L Misset, and M Itzhaki, and R Adam, and G Milano, and B Hecquet, and G Mathé
Phase-I trial of combination therapy with continuous-infusion MMPR and continuous-infusion 5-FU.
January 1984, Cancer chemotherapy and pharmacology,
Copied contents to your clipboard!