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C Focan

Publications and source records attributed to C Focan.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Chronopharmacologic approach to the administration of anticancer agents in pancreatic adenocarcinoma. Pilot experience].

The authors first analyzed the potential interest of the delivery of anticancer agents according to chronobiological concepts for human pancreatic cancer. They report their experience on 41 patients treated in adjuvant (12 cases) or palliative (29 cases) situations. The excellent therapeutic index observed warrants further evaluations of this concept in randomized trials.

Adenocarcinoma↗
PubMed1999

A multicenter evaluation of intensified, ambulatory, chronomodulated chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin as initial treatment of patients with metastatic colorectal carcinoma. International Organization for Cancer Chronotherapy.

BACKGROUND: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. This allowed the authors to intensify the three-drug chronotherapy regimen and to assess its activity as the initial treatment of metastatic colorectal carcinoma patients in ten centers from four countries. METHODS: Patients with previously untreated and inoperable measurable metastases from colorectal carcinoma received a daily administration of chronomodulated 5-FU (700 mg/m2/day, peak delivery rate at 04:00 hours), LV (300 mg/m2/day, peak delivery rate at 04:00 hours), and 1-OHP (25 mg/m2/day, peak delivery rate at 16:00 hours) for 4 days every 14 days. Intrapatient escalation of 5-FU dose was performed if toxicity was less than World Health Organization (WHO) Grade 2. RESULTS: Of 90 enrolled patients, 35 had a WHO performance status of 1 or 2; 49 had metastases in > or = 2 organs. The liver was involved in 79 patients, 30 of whom had clinical hepatomegaly. The main dose-limiting toxicities were WHO modified Grade 3 or 4 diarrhea (41% of patients, 8.2% of courses), stomatitis (30% of patients, 5.1% of courses), and Grade 2 cumulative peripheral sensory neuropathy (19% of patients after 12 courses). Two patients died with severe gastrointestinal toxicity. Using the intent-to-treat method, the overall objective response rate was 66% (95% confidence limits, 56-76%). Surgical removal of previously inoperable metastases was successful in 31 patients (34%). Histologic necrosis of metastases was >90% in 7 patients and complete in 1 patient. The median progression free survival and survival durations were 8.4 months (range, 5.9-10.9 months) and 18.5 months (range, 13.2-23.8 months), respectively, with 38% of the patients alive at 2 years of follow-up. CONCLUSIONS: The objective response rate appeared to be approximately 3-fold as high as that achieved with current 5-FU-based regimens and translated into an approximately 50% increase in median survival. The hypothesis that this intensified, ambulatory, chronotherapy regimen can increase survival currently is being investigated in a multicenter randomized study conducted by the European Organization for Research and Treatment of Cancer Chronotherapy Study Group.

Aged↗
PubMed1999

Continuous delivery of venous 5-fluorouracil and arterial 5-fluorodeoxyuridine for hepatic metastases from colorectal cancer: feasibility and tolerance in a randomized phase II trial comparing flat versus chronomodulated infusion.

High-dose chemotherapy combining regional hepatic artery infusion (HAI) of fluorodeoxyuridine (HAI FUDR) and systemic venous infusion of 5-fluorouracil (i.v. 5-FU) was delivered against liver metastases from colorectal cancer. The hypothesis that chronomodulation of delivery rate along the 24 h time scale would improve the tolerable doses of both drugs was tested. Combined HAI FUDR (80 mg/m2/day) and i.v. 5-FU (1200 mg/m2/day) were administered for five consecutive days every 3 weeks, either as a constant rate infusion (schedule A, 27 patients) or as chronotherapy (schedule B, 29 patients). This latter regimen consisted of a sinusoidal modulation of the delivery rate over the 24 h scale with a maximum at 16:00 for FUDR and 4:00 for 5-FU. Intrapatient dose escalation up to the individual maximum tolerated doses (MTD) was planned for both drugs in the absence of any previous grade 3 or 4 toxicity. All patients had metastatic colorectal cancer, with adjuvant or palliative chemotherapy given to six patients (22%) on schedule A and 12 patients on schedule B (41%). Severe stomatitis occurred in 71% of the patients and was dose limiting. No hepatic toxicity was encountered. Dose reductions of 5-FU and/or FUDR were required for 17 of 27 patients on schedule A (63%) as compared to 11 of 29 patients on schedule B (38%), following reaching the individual MTD (p<0.05). Over the first six cycles, patients on schedule B received higher doses (mg/m2/cycle; FUDR: 522 +/- 85 versus 499 +/- 50, p=0.004 and 5-FU: 5393 +/- 962 versus 5136 +/- 963, p=0.009) and higher dose intensities (mg/m2/week; FUDR: 164 +/- 46 versus 151 +/- 52, p=0.018 and 5-FU: 1652 +/- 478 versus 1553 +/- 535, p<0.041) of both drugs than patients on schedule A. As a result the number of courses with doses of 5-FU above 1200 mg/m2/day and/or FUDR above 110 mg/m2/day was larger in group B than in group A (5-FU, A: 67 of 268, 25% versus B: 133 of 321, 41% and FUDR, A: 86 of 268, 32% versus B: 155 of 321, 48%; p<0.001). Objective responses were observed in 13 patients on schedule A (48%) and 11 patients on schedule B (38%). The results support the need for further exploration of chronotherapy of colorectal cancer liver metastases with combined arterial and venous fluoropyrimidine chemotherapy.

Adult↗
PubMed1998

[Clinical case of the month. Metastatic endocarditis: clinical observation and review of the literature].

The authors describe a case of metastatic endocarditis associated with a gastric carcinoma. The diagnosis was made early and the treatment by surgery and chemotherapy allowed a survival of 18 months, which is unusually long. The differential diagnosis is discussed and includes nonbacterial thrombotic endocarditis, infectious endocarditis and primary tumors of the heart.

Adenocarcinoma↗
PubMed1995

Circadian rhythms and cancer chemotherapy.

Experimental and clinical pertinent data regarding circadian rhythmicities are reviewed in (1) target tissues, i.e., healthy tissues (actively proliferating or not) and tumor tissues, (2) pharmacology of anticancer agents, (3) toxicity and tolerance of these agents and (4) antitumor activity of cancer chemotherapy. The basic concepts of chronotolerance and/or of chronoefficacy have brought new hopes for further amelioration in the management of cancer patients. Quite recent published Phase II and III clinical trials have demonstrated that new improvements on the therapeutic index have been achieved through ambulatory chronotherapy for various solid tumors.

Animals↗
PubMed1995

Ambulatory chronotherapy with 5-fluorouracil, folinic acid, and carboplatin for advanced non-small cell lung cancer. A phase II feasibility trial.

Thirty-two patients with advanced non-small cell lung carcinoma (NSCLC) received a chronomodulated 5-day venous infusion of 5-fluorouracil (5 FU) (700 mg/m2/day), folinic acid (F) (300 mg/m2/day), and carboplatin (C) (40, 50, or 55 mg/m2/day), as first chemotherapy. Courses were repeated every 21 days (after a 16-day interval). In total, 158 courses (median: 4, range: 1 through 16; 81 and 58 courses at, respectively, a 40 and 50 to 55 mg/m2 daily dosage of C) were delivered using a multichannel programmable in-time pump (Intelliject, Aguettant) connected to a double lumen implanted venous side-port. The administration was allowed in fully ambulatory convenience. Overall tolerance was excellent. Grade 3 of 4 hematologic toxicity was encountered in 4.6% of courses for thrombopenia and in 7.0% of courses for neutropenia. Nausea or vomiting (grade 3 or 4) occurred in 7.8% of courses. Mucositis, diarrhea, alopecia, or skin grade 3 or 4 toxicity were observed in less than 3% of courses. Treatment delay was needed in only 7.8% of courses and dose reductions were needed in 4.6% of courses for 5 FU and in 6.5% of courses for C. This good tolerance allowed a sustained quality of life and prompted further trials aiming to define the place of this protocol in the multidisciplinary treatment approach of NSCLC.

Adult↗
PubMed1994

Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial.

BACKGROUND: In a previous phase II trial, circadian (chronomodulated) delivery of fluorouracil (5-FU), folinic acid (FA; leucovorin), and oxaliplatin (1-OHP; a new platinum complex with no renal and minor hematologic toxic effects) produced an objective response rate of 58% in 93 patients with metastatic colorectal cancer. PURPOSE: To determine whether chronomodulated drug delivery affects therapeutic activity, we again tested this regimen in another trial in patients with previously untreated metastatic colorectal cancer, this time comparing chronomodulated with constant-rate drug delivery. METHODS: Seven European centers participated in this trial. Ninety-two patients with metastatic colorectal cancer were enrolled and assigned to a treatment schedule by central randomization. Treatment courses consisted of the daily administration of 5-FU (600 mg/m2 per day), FA (300 mg/m2 per day), and 1-OHP (20 mg/m2 per day) for 5 days and were repeated every 21 days (16-day intermission) in ambulatory patients with the use of a programmable in-time pump. Drug delivery was kept constant over a 5-day period in schedule A (47 patients). It was chronomodulated in schedule B (maximum delivery of 5-FU and FA infusions at 0400 hours and maximum delivery of 1-OHP at 1600 hours; 45 patients). A risk of partial chemical inactivation of 1-OHP by its 2-hour exposure to the basic pH of the 5-FU solution in the catheter was documented in schedule A. RESULTS: Severe stomatitis (grade 3 or 4, World Health Organization [WHO] grading system), the dose-limiting toxic effect of 5-FU, occurred in five times as many patients on schedule A than on schedule B (89% versus 18%; chi 2 = 46; P < .001). The cumulative dose-limiting toxicity of schedule B was peripheral sensitive neuropathy (WHO grade 2). This side effect was reversible following 1-OHP withdrawal. Higher doses of 5-FU were administered in schedule B (median: 700 mg/m2 per day) compared with schedule A (median: 500 mg/m2 per day) (P < .0001; Mann-Whitney U test). On schedule B, 24 of 45 patients (53%; 95% confidence interval [CI] = 38%-68%) exhibited an objective response compared with 15 of 47 patients (32%; 95% CI = 18%-46%) on schedule A (chi 2 = 4.3; P = .038). The median progression-free survival was, respectively, 11 and 8 months (P = .19; logrank). The median survival was 19 months (95% CI = 14.8-23.2) on schedule B and 14.9 months (95% CI = 12.1-17.8) on schedule A (P = .03; logrank). CONCLUSION: This ambulatory treatment modality was both more effective and less toxic if drug delivery was chronomodulated rather than constant over time. IMPLICATION: The respective roles of 1-OHP dose and schedule and circadian peak time of drug delivery are being investigated with regard to the high activity of this three-drug, chronomodulated chemotherapeutic regimen.

Adult↗
PubMed1993

Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate.

Oxaliplatin (L-OHP) is a non-nephrotoxic third generation platinum complex with proven antitumoral activity and minimal haematological toxicity. Circadian scheduling has allowed significant increases in L-OHP dosage and dose intensity and decreases in its toxicities. This phase II trial has tested the antitumour activity of a 5-day circadian schedule of continuous venous infusion of L-OHP against metastatic colorectal cancer. Initial dose was 150 mg/m2/course. An intrapatient dose escalation scheme by 25 mg/m2/course was planned up to 200 mg/m2/course, according to toxicity criteria. The delivery rate of L-OHP was sinusoidally modulated along the 24-h time scale, and was highest at 1600 h. A programmable-in-time ambulatory pump was used, so that all patients could receive their treatment at home. 29 of 30 patients registered were eligible. 25 had failed previous chemotherapy. Three objective responses were observed (response rate: 10%), in patients progressive while on chemotherapy with 5-fluorouracil and folinic acid. Toxicity was moderate. Dose-limiting toxicities were diarrhoea and peripheral sensitive neuropathy. The latter adverse effect appeared to be cumulative. L-OHP, as delivered under this circadian schedule, exhibits clinical antitumour activity against metastatic colorectal cancer. These results, which await further confirmation, support the place of L-OHP in combination regimens including 5-fluorouracil.

Adult↗
PubMed1993

Ambulatory treatment with 5 days continuous venous infusion of ifosfamide for advanced colorectal cancer: a phase II feasibility study.

Eighteen patients suffering from an advanced colorectal cancer were treated with 5 days continuous venous infusion of ifosfamide and mesna (1 g/m2, 5/21 days). All had previously received 5-fluorouracil-based chemotherapies. Disposable programmable infusion pumps (Cadd-I, Pharmacia Deltec and Intelliject Multisyringe) allowed ambulatory administration of the treatment. Toxicity was manageable; we had mainly to deplore two cases of grade 3 central nervous system manifestations. Only one minor response (lung lesions) and one no change were evidenced. We conclude that for this type of patient, ifosfamide has very limited antitumor activity. Nevertheless, we demonstrated the safety and feasibility of the proposed ambulatory schedule which could be used in other oncological indications.

Adult↗
PubMed1993

Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: a prospective randomized trial.

PURPOSE: We compared prospectively the antitumor efficacy of two combination chemotherapy regimens with two different dose levels of epirubicin as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: One hundred forty-one fully assessable patients were randomized to receive either our intensified schedule (group A, n = 71) of epirubicin 50 mg/m2 on days 1 and 8 (every 3 weeks), or a non-intensified program (group B, n = 70) in which epirubicin was only administered on day 1. Both groups also received fluorouracil (5 FU) and cyclophosphamide 500 mg/m2 on day 1 of each course. RESULTS: A statistically significant difference in response rate was observed (69% in group A v 41% in group B, P < .001) for both locally advanced (LA) and recurrent metastatic (RM) disease. Response duration (22 v 14 months, P < .01) and time to progression (TTP; 19 v 8 months, P < .02) were also significantly improved. Overall survival was similar in both groups. However, univariate and/or multivariate analyses showed a meaningful relationship between type of treatment allocated, dose-intensity (DI) of epirubicin, and response rate, as well as between TTP and survival. Ultimately, TTP and survival were also influenced by further treatment modalities, namely, hormonotherapy and chemotherapy. CONCLUSION: This study validates prospectively the concept of a dose-response relationship for an anthracycline-based chemotherapy in previously untreated advanced breast cancer.

Actuarial Analysis↗
PubMed1992

[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients].

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.

Adult↗
PubMed1991

Oral administration of [3H]navelbine in patients: comparative pharmacokinetics using radioactive and radioimmunologic determination methods.

[3H]Navelbine (NVB) was administered orally to two patients. Drug levels in biological fluids were monitored by radioimmunoassay (RIA) and direct radioactivity (RA) determinations. NVB absorption was rapid: maximum plasma concentrations appeared in the first 2 h after oral administrations. Pharmacokinetic parameters estimated from RIA data were in complete accordance with those obtained from i.v. injections. Bioavailability (i.v./po) estimated from RIA and RA data averaged 40.6 and 93.0%, respectively. NVB urine excretion was low. Fecal excretion remained its main elimination route. Moreover, large differences were observed in area under NVB plasma concentration-time curve (AUC) values obtained by the two methods, implying intense drug bio-transformations.

Administration, Oral↗
PubMed1990

Experience of the Belgian Society of Medical Oncology with single-administration 5 g/m2 ifosfamide with mesna as second- or third-line therapy in advanced breast cancer.

In an ongoing phase II trial conducted in advanced breast cancer, we tested a therapy schedule consisting of continuous, 24-h infusion of 5 g/m2 ifosfamide (IFO) in 3 1 dextrose saline with mesna (MSN), repeated every 3 weeks until disease progression. Since September 1988, 16 heavily pretreated patients with advanced disease (11 with visceral lesions) considered refractory to standard chemotherapy (regimens always including cyclophosphamide) have been included. Objective partial remissions were observed in two cases (one in liver and one in soft-tissue and pleural lesions), and disease stabilization for at least 3 months occurred in four cases. No treatment-related death was recorded and tolerance was judged to be excellent (six cases) or acceptable in all instances. The haematological toxicity consisted mainly of transient leucopenia (nadirs evaluated by WHO scale as grade 3 in 43% and grade 4 in 29%), sometimes associated with thrombocytopenia (grade 3 in 7% and grade 4 in 7%). Other side effects included nausea and/or vomiting (grade 3-4 in 33%); worsening of preexisting alopecia (five cases); haemorrhagic cystitis (one case); mild, transient somnolence (two cases); and moderate fluid retention (two cases). We concluded that infusion of 5 g/m2 IFO over 24 h with MSN rescue might represent an acceptable second- or third-line salvage regimen. Close monitoring of haematological and renal function parameters is recommended. A larger number of patients will be treated in a continuation of this study to evaluate the true response rate within narrower confidence limits.

Adult↗