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D Perrault

Publications and source records attributed to D Perrault.

10 recordsLinked to original sources

The Canadian experience with intensive fluorouracil, epirubicin and cyclophosphamide in patients with early stage breast cancer.

A multicentre dose-finding pilot study was conducted to determine an intensive regimen of fluorouracil (F), epirubicin (E) plus cyclophosphamide (C) [FEC] that was tolerable and acceptable to patients with node-positive operable (n = 266) or locally advanced (n = 22) breast cancer. Consecutive patients were treated with fluorouracil and epirubicin administered intravenously on days 1 and 8, in addition to cyclophosphamide orally for 14 days. Chemotherapy cycles were repeated at monthly intervals for 6 months, and dosages were increased according to a predetermined protocol. End-points were hospital admissions due to febrile neutropenia and changes in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated with doses of F = 375 mg/m2, E = 50 mg/m2 and C = 75 mg/m2 (level 1), then 42 patients received F = 500 mg/m2, E = 50 mg/m2 and C = 75 mg/m2 (level 2), 69 patients received F = 500 mg/m2, E = 60 mg/m2 and C = 75 mg/m2 (level 3), and 42 patients received F = 500 mg/m2, E = 70 mg/m2 and C = 75 mg/m2 with concurrent antibiotics (level 4). Rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4) [p = 0.002]. Accrual to level 4 was discontinued according to study protocol and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between dosage levels 3 and 3a was statistically significant (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

A pilot study of intensive cyclophosphamide, epirubicin and fluorouracil in patients with axillary node positive or locally advanced breast cancer.

A multicentre pilot study has been conducted to determine an intensive regimen of cyclophosphamide, epirubicin, and fluorouracil which was tolerable and acceptable to patients with node positive breast cancer. Consecutive patients with operable axillary node positive breast cancer (T1-3, N1-2, M0), 266 patients, or locally advanced breast cancer (T4), 22 patients, were treated with cyclophosphamide post-operatively for 14 days and epirubicin and fluorouracil, both intravenously on days 1 and 8. Each cycle was repeated monthly for 6 months. Dosages were increased according to predetermined guidelines. Outcome measures were admission to hospital for febrile neutropenia and change in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated at the doses of cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2, fluorouracil = 375 mg/m2 (level 1), then 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2 and fluorouracil = 500 mg/m2 (level 2), 69 patients at cyclophosphamide = 75 mg/m2, epirubicin = 60 mg/m2, and fluorouracil = 500 mg/m2 (level 3), and 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 70 mg/m2, and fluorouracil = 500 mg/m2 with concurrent antibiotics (level 4). The rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4), respectively, P = 0.002. Accrual to level 4 was discontinued according to study guidelines and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between levels 3 and 3a was statistically significant. There were no toxic deaths and 2 cases of heart failure. In conclusion, through a careful dose-finding study in patients with operable or locally advanced breast cancer, an intensive epirubicin-containing adjuvant regimen has been established which is presently being compared with standard CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy in a randomised trial. In addition, this study suggests that antibiotic prophylaxis reduces the risk of febrile neutropenia in breast cancer patients receiving intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Phase I study of weekly intravenous administration of menogaril to adults with solid tumors.

Thirty-nine adults with solid tumors were treated on a Phase I study of menogaril administered i.v. once each week. Granulocytopenia was dose-limiting at a menogaril dose of 115 mg/m2/wk. Ten patients required delays in treatment of 1-4 weeks (median, 1 week) at some point during their treatment until they recovered from granulocytopenia. The average dose intensity possible on this schedule was at least 80% higher than that possible using a single-day or a five-times-daily schedule every 4 weeks. One patient developed infection while neutropenic, and only one patient developed thrombocytopenia. Dexamethasone appeared to reduce the degree of myelosuppression. Gastrointestinal toxicity was quite mild, and alopecia was uncommon. Arm vein phlebitis frequently followed menogaril administration, requiring the use of Hickman catheters (or equivalents). Two patients had myocardial infarcts while on treatment. It was unclear if the menogaril was in any way responsible. Reversible dyspnea and cough (with no evidence of congestive heart failure) were seen in some patients. Responses were seen in patients with gliomas, renal-cell carcinoma, and bladder carcinoma, and marked subjective improvement occurred in a single patient with prostate cancer. We plan to conduct a Phase II study in astrocytoma patients using a menogaril dose of 115 mg/m2/wk i.v.

Adult

A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

A randomized comparison of cyclophosphamide-mitoxantrone-5-fluorouracil v cyclophosphamide-doxorubicin-5-fluorouracil in advanced breast cancer: preliminary observations.

Forty-four patients with measurable metastatic breast cancer have been entered in a randomized study comparing mitoxantrone to doxorubicin as a component of front-line combination chemotherapy. Patients were stratified according to whether or not they had previously received adjuvant chemotherapy. Initial doses of cyclophosphamide and 5-fluorouracil were 500 mg/m2 for both regimens, with either mitoxantrone, 10 mg/m2, or doxorubicin, 50 mg/m2. All drugs were given on day 1 only, with treatments repeated every 3 weeks. Doses were adjusted according to blood count nadirs. Responses have been observed in both of the treatment groups, though it is too early to determine the relative efficacy of the two regimens. Toxicity was comparable on the two treatment regimens except that far less alopecia and stomatitis were associated with the mitoxantrone therapy. No congestive heart failure has been seen. The combination of cyclophosphamide-mitoxantrone-5-fluorouracil is reasonably well tolerated, with myelosuppression being dose limiting. In both treatment groups of this study, reliance on the leucocyte count, rather than the granulocyte count, as a basis for dose alteration or treatment delay would lead to excessive dose reductions, many fewer dose escalations, and much more treatment delay.

Anthraquinones

Results of treating Hodgkin's disease without a policy of laparotomy staging.

Results of the treatment of 780 primary patients with Hodgkin's disease at the Princess Margaret Hospital (PMH) between 1968 and 1977 are analyzed. Treatment decisions were based on the evaluation of the extent of disease by clinical methods. A marked improvement in relapse-free survival and overall survival was observed for 1973-1977 as compared to 1968-1972. This improvement did not result from differences in the distribution of important prognostic attributes (clinical stage, pathology, and age) between the two periods, and there was no improvement in our ability to rescue relapsed patients. Improved relapse-free and overall survival during the second period was observed for all stages in patients less than 50 years of age, but not in the older group. The improved survival of patients treated between 1973 and 1977 is attributed to more effective initial therapy, which reduced the fraction of patients who relapsed. These observations provide indirect evidence that relapse has a negative effect on prognosis, and that the initial treatment of patients with Hodgkin's disease should be designed to reduce the risk of relapse to a minimum without causing an unacceptable increase in late complications. The observed/expected incidence of acute leukemia and non-Hodgkin's lymphoma in the PMH series was increased to 41.9 and 13.9 respectively. The question of whether a policy of doing routine staging laparotomies improves the results of treatment of patients with Hodgkin's disease is considered only in general terms by comparing the total PMH series with the total Stanford Medical Center series of patients treated between 1968 and 1977. Relapse-free survival at 10 years is 48.9% and 66.8% respectively, at the two institutions, while overall survival at 10 years is identified.

Adult

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Canada