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Biomedical subjects

M Piccart

Publications and source records attributed to M Piccart.

At least 91 records · Page 5Linked to original sources
PubMed1994

A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer. A study of the EORTC Early Clinical Trials Group.

BACKGROUND: Docetaxel, a semisynthetic analog of paclitaxel, made for the needles of the European yew, Taxus baccata, is a potentially important chemotherapeutic agent for the treatment of cancer. PATIENTS AND METHODS: In a phase II study patients with advanced and/or metastatic breast cancer and bidimensionally measurable disease, were treated with docetaxel 100 mg/m2 every 3 weeks as a 1 hour infusion without any premedication. Treatment was evaluated after 2 courses and every 2 subsequent courses. RESULTS: Thirty-nine patients were entered, 32 were eligible. The eligible patients had a median age of 51 years (range 30-73) and a performance status WHO 1 median, (range 0-2). Twenty-eight patients had been treated with surgery, 24 with radiation. Hormonal treatment was previously given in 23, chemotherapy in 32. Of 24 patients treated as second line strategy, 13 achieved a partial remission, 1 a complete remission (overall response rate 58% (95% CI 37%-78%)). Eight patients treated as first line: 2 PR's, 1 CR. The median overall response duration was 38 weeks. The main toxicity consisted of transient grade 4 neutropenia in 149 of 167 evaluable courses (89%). However, the related infection rate was low. Re-treatment at 3 weeks, as scheduled, was nearly always possible. Other toxicities consisted of skin reactions (81%) and nail changes (41%), neurosensory toxicity (59%) and occasionally hypersensitivity reactions (16%). Fluid retention was a toxicity of major concern, observed in 59% of patients. CONCLUSION: Docetaxel is a very active drug against breast cancer. Further studies are required to alleviate the non-hematological toxicities.

Adult↗
PubMed1993

Routine follow-up of patients after primary therapy for early breast cancer: changing concepts and challenges for the future.

In an era of increasing financial constraints, physicians are being forced to critically re-evaluate various clinical practices that have not been shown to be cost-effective or associated with definitive patient benefit. Routine follow-up programs following primary therapy for early-stage breast cancer vary widely from centre to centre, and although the subject of numerous retrospective analyses, they have not been prospectively evaluated to date. This review paper presents arguments for changing the emphasis of follow-up visits and stresses the need for prospective clinical and cost-benefit evaluations of current follow-up practices.

Breast Neoplasms↗
PubMed1993

Successful re-treatment with taxol after major hypersensitivity reactions.

PURPOSE: To describe the successful re-treatment of eight patients who had major hypersensitivity reactions (HSRs) to taxol and to suggest a regimen for re-treating patients who develop major HSRs. PATIENTS AND METHODS: The treatment courses of eight patients who developed major HSRs and were rechallenged with taxol were reviewed. Patients in this report represent all patients who are known to have been rechallenged with taxol after major HSRs. RESULTS: The most common approach used to rechallenge patients consisted of premedication with multiple high doses of corticosteroids and H1- and H2-histamine antagonists followed by the initiation of the taxol infusion at a reduced rate. All patients who experienced major HSRs were rechallenged successfully. After the rechallenge, these patients received 32 additional courses of taxol without HSRs. CONCLUSION: Re-treatment with taxol after major HSRs is feasible using multiple high doses of corticosteroids and antihistamine premedications and a reduced taxol infusion rate under close supervision. This approach may represent a valid alternative to the termination of taxol; however, a prospective evaluation is required to determine the true efficacy of this approach.

Aged↗
PubMed1993

Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam.

PURPOSE AND METHODS: Although a high prevalence of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy (CT) has been reported, little has been done to develop strategies to prevent these problems. A double-blind, placebo-controlled study was therefore designed to assess the usefulness of adding low-dose alprazolam (0.5 mg to 2 mg per day) to a psychologic support program including progressive relaxation training designed to prevent the aforementioned conditions. Fifty-seven women undergoing adjuvant CT for stage II primary breast cancer agreed to participate in the assessment, which was conducted at four time points: before starting CT, 6 weeks after CT, before the fourth CT, and after the fourth CT. The Hospital Anxiety and Depression Scale (HADS), Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAS), Revised Symptom Checklist (SCL-90-R), Morrow Assessment of Nausea and Emesis (MANE), and World Health Organization (WHO) grading of acute and subacute toxicities were used to compare the alprazolam (AA) and placebo (PA) arms of the study. RESULTS: At the second evaluation, the results showed a higher rate of anticipatory nausea (18% v 0%) in the PA compared with the AA arm (P = .038). These differences were no more significant at each of the further assessments. Significant differences were found for the intake of hypnotics at each assessment visit, with the rate of hypnotic users being significantly higher in the PA (19%) compared with the AA (0%) arm at the fourth assessment (P < .05). Anxiety and depression scores of self- and observer-report were similar in the two arms. A significant relationship was found between the development of anticipatory nausea and the self-report of anxiety and depression score measured by HADS at baseline. The average HADS total score at baseline was 15.33 (SD = 6.56) for patients who developed anticipatory nausea and 11.23 (SD = 6.67) for other patients. CONCLUSION: The adjunct of alprazolam to a psychologic support program delays the occurrence of anticipatory nausea and controls sleeping problems secondary to adjunct CT. Although studies are needed to improve the efficacy reported here, physicians may already consider the use of alprazolam for cancer patients undergoing CT.

Adjustment Disorders↗
PubMed1992

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Adolescent↗
PubMed1991

Phase I clinical and pharmacokinetic study of zeniplatin, a new platinum complex.

Forty-six patients with refractory solid malignancies received the new platinum complex [2,2-bis(aminomethyl)-1,3-propanediol-N-N'] [1,1-cyclobutanedicarboxylato] [(2-)0,0')] platinum (zeniplatin). Zeniplatin was given, without hydration or mannitol, as a 60- to 90-min i.v. infusion every 3 weeks at doses ranging from 8 to 145 mg/m2. The maximum tolerated dose of zeniplatin was 145 mg/m2. The dose-limiting toxicity of zeniplatin was dose-related leukopenia and neutropenia, with the nadir usually observed between 1 and 2 weeks after therapy and recovery usually occurring by 3 weeks after therapy. Thrombocytopenia was rare. The most prominent non-hematological side-effect of zeniplatin was nausea and vomiting. Other non-hematological side-effects were mild or absent. Zeniplatin did not induce significant neurological or auditory toxicity. Zeniplatin was not nephrotoxic at doses less than or equal to 120 mg/m2. At 145 mg/m2, the clearance decreased by a mean of 40% after 2 cycles of therapy. Two patients, one with malignant melanoma and one with renal cell cancer, achieved a partial response. Pharmacokinetics of free (plasma ultrafiltrates) and total platinum in plasma were determined in 5 patients. An in vitro study of the rate and extent of zeniplatin binding to protein in human plasma was also performed. Free and total platinum were measured by flameless atomic absorption spectrometry; free zeniplatin was measured in ultrafiltrate by HPLC. Total and free plasma platinum concentrations were co-modelled using the information from the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1990

Therapy of infections related to intraperitoneal catheters in patients with ovarian cancer.

Bacterial peritonitis is a common complication associated with catheters implanted for intraperitoneal anticancer chemotherapy in patients with extensive ovarian carcinoma. During an ongoing trial of intraperitoneal cisplatin-melphalan vs. cisplatin-gamma interferon, given via an intraperitoneal 'Port-a-cath' catheter, 6 episodes of suspected bacterial peritonitis occurred in 5 patients. Clinical symptoms were present in all episodes and 3 episodes were documented microbiologically. Teicoplanin was given intraperitoneally, 400 mg three times a day on the first day and once daily thereafter. Serum and peritoneal concentrations were measured by bioassay. Despite clinical improvement during therapy, the catheter was removed in 4 out of 5 patients after the end of intraperitoneal teicoplanin, due to the presence of infection. Additional patients are required to evaluate the efficacy of intraperitoneal teicoplanin in the treatment of catheter-related peritonitis associated with anticancer intraperitoneal chemotherapy.

Aged↗
PubMed1990

Lethal anuria complicating high dose ifosfamide chemotherapy in a breast cancer patient with an impaired renal function.

A sixty-year-old woman with advanced breast cancer, previously treated with cisplatin, developed an irreversible lethal renal failure with anuria, the day after 5 g/m2 bolus ifosfamide. Postrenal failure was excluded by echography. A prerenal component could have contributed to renal failure because of a transient hypotension, due to an increasing ascitis, occurring just before anuria. However, correction of the hemodynamic parameters did not improve renal function. Ifosfamide is a known nephrotoxic drug with demonstrated tubulopathies. We strongly suspect that this lethal anuria was mainly due to ifosfamide, occurring in a patient having received previous cisplatin chemotherapy and with poor kidney perfusion due to transient hypotension. We recommend careful use of ifosfamide in patients pretreated with nephrotoxic chemotherapy and inadequate renal perfusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗
PubMed1989

Phase II trial of mitozolomide in patients with advanced ovarian cancer. A study of the EORTC Gynecological Cancer Cooperative Group.

Twenty-seven fully evaluable patients with advanced ovarian cancer and documented disease progression despite cytotoxic treatment were treated with mitozolomide (NCS-353451) 90 mg/m2 as a 1-h infusion once every 6 weeks. None of the patients responded, one had stabilization of disease for 4 months. Haematologic toxicity was the major side effect with a nadir or white blood cell counts around day 40. Two patients died with severe leukopenia and septic shock. We conclude that mitozolomide is not active in this poor-risk group of patients.

Adult↗
PubMed1988

Ureteral obstruction in patients with breast cancer.

Six breast cancer patients were treated recently for renal insufficiency secondary to neoplasic involvement of the ureters. This complication usually occurs in long standing hormonal-dependent breast cancer with bone metastases. Diagnosis was performed by abdominal echography. Ureteral catheterization or percutaneous nephrostomy with or without irradiation always resulted in rapid recovery of renal function. Systemic chemotherapy could then be given, sometimes with antitumoral responses, allowing the removal of the endoureteral catheters.

Acute Kidney Injury↗
PubMed1988

Phase I clinical and pharmacokinetic trial of oral menogaril administered on three consecutive days.

Eighteen adult patients with solid tumors were treated with oral menogaril, a new anthracycline antibiotic active against human breast cancer after intravenous administration. The drug was given orally on 3 consecutive days every 4 weeks at doses ranging from 50 to 175 mg/m2/day. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal usually 2 weeks after treatment and recovery usually occurred within 4 weeks. At doses from 50 to 150 mg/m2/day, non-hematologic side-effects of oral menogaril were infrequent and mild and consisted of nausea and vomiting (one patient), alopecia (two patients), mucositis (two patients) and liver function test abnormalities (three patients). The single patient treated at a daily dose of 175 mg/m2/day developed grade IV leucothrombocytopenia, with fever and gastrointestinal bleeding. This was followed by heart failure and the patient died from multisystem organ failure. Peak plasma concentrations of menogaril ranged from 0.043 to 0.409 microM and were linearly correlated with the dose. Similarly, the area under the plasma concentration versus time curve varied from 0.33 to 9.59 microM X h and was linearly correlated with the dose. The mean harmonic half-life was 11.3 +/- 6.4 h. A comparison of the data from the present trial and our previous study with intravenous menogaril indicates a bioavailability of 32 +/- 12%. There was an excellent relationship between the white blood cell decrease (as a percentage of the pretreatment value) and several pharmacokinetic parameters; the best correlation was obtained with the plasma concentration of menogaril at 4 h after treatment. A dose of 150 mg/m2/day for 3 consecutive days is recommended for phase II trials with oral menogaril but the bioavailability of the drug should be monitored carefully and, more specifically, the concept of a pharmacokinetic adjustment of the dose of menogaril should be evaluated prospectively.

Administration, Oral↗
PubMed1984

Single-drug versus combination empirical therapy for gram-negative bacillary infections in febrile cancer patients with and without granulocytopenia.

Empirical therapy with cefoperazone was compared with cefoperazone plus amikacin in granulocytopenic and nongranulocytopenic febrile patients. In nonneutropenic patients the overall response rate to cefoperazone was 88%; 10 of 12 gram-negative bacteremic patients were cured. Cefoperazone plus amikacin resulted in an 88% overall response rate and cured 14 of 15 patients with bacteremia. In neutropenic patients the overall response rate was 77% with cefoperazone alone and 73% with cefoperazone plus amikacin; the cure rates for gram-negative bacteremias were 8 of 11 and 6 of 12 patients, respectively. Our findings support the concept of single-drug empirical therapy with cefoperazone in febrile cancer patients, whether granulocytopenic or not, especially when gram-negative bacteremias are predominantly caused by Escherichia coli or Klebsiella species. The issue of Pseudomonas spp. and other more resistant pathogens needs further assessment with a larger number of patients.

Adolescent↗
PubMed1983

Clinical phase I trial of marcellomycin with a single-dose schedule.

Marcellomycin is a new anthracycline that was proposed for clinical trials on the basis of experimental data suggesting reduced potential for hematologic and cardiac toxicity as compared to conventional anthracyclines. This phase I trial was designed to determine the maximum tolerated dose of marcellomycin at a single-dose schedule. The drug was given as a 15-to 30-min i.v. injection. Eighteen patients with a variety of solid tumors received a median of 2 courses (range: 1-5) at doses of 5-60 mg/m2. Myelosuppression was dose-limiting and somewhat unpredictable. It was characterized by early thrombocytopenia and late leukopenia. It occurred at doses greater than or equal to 40 mg/m2 and resulted in a few cases of infection and hemorrhage. Nausea, vomiting and stomatitis were frequent and occasionally severe. Other common non-hematological toxic effects consisted of local phlebitis and fatigue. Electrocardiographic changes were also encountered. Hair loss was rare and negligible. No antitumor activity could be detected. It appears that phase II trials should be preferably restricted to ambulatory patients and that a dose schedule of 50 mg/m2 repeated every 3 weeks may be proposed for this favorable patient population.

Adult↗