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P Rebattu

Publications and source records attributed to P Rebattu.

At least 19 recordsLinked to original sources
PubMed2005

Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin.

BACKGROUND: This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine-docetaxel (GD) combination versus cisplatin-vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m(2) days 1 and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), days 1, 8, 15 and 22, every 4 weeks for six cycles). RESULTS: A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83-1.32], and for overall survival, it was 0.90 (95% CI 0.70-1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. CONCLUSIONS: There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.

Adult↗
PubMed2004

[Do combinations without cisplatin represent an alternative to conventional chemotherapy in non-small cell lung cancers?].

Chemotherapy of advanced non-small cell lung cancers is based on cisplatin, which prolongs survival. However, the high toxicity of double-type combinations including cisplatin warrants the search for alternatives. New anti-cancer cytotoxic agents exhibit improved efficacy-toxicity ratio. Bitherapy, without cisplatin and with new molecules, provides hope of improvement in survival without deterioration in quality of life. Several randomised trials, already published or presented with mature results, suggest that certain bitherapies with new cytostatic agents are an alternative to the classical cisplatin-based bitherapies. The recent modifications in the guidelines of the American Association of Clinical Oncology take into account these recent results by admitting that "chemotherapy without cisplatin can be used as an alternative to the first-line platin-based chemotherapies". This brief review of the literature underlines the methodological questions raised by the publication of randomised studies essentially assessing gemcitabine-vinorelbine or gemcitabine-taxane combinations, by confronting them with either mono-chemotherapies or reference chemotherapy based on cisplatin. The assessment criteria selected in such studies are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients.

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m(-2)) and cyclophosphamide (2 g m(-2)) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m(-2) and thiotepa 200 mg m(-2). At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m(-2) cyclophosphamide and 400 mg m(-2) thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immunosuppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.

Adult↗
PubMed2001

Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1.

PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

Adult↗
PubMed2000

In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.

PURPOSE: The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS: Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). RESULTS: Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. CONCLUSIONS: Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

Aged↗
PubMed2000

Population pharmacokinetics of doxorubicin, etoposide and ifosfamide in small cell lung cancer patients: results of a multicentre study.

AIMS: To determine the population pharmacokinetic (PK) parameters of doxorubicin (Dox), etoposide (Eto) and ifosfamide (Ifo) in small cell lung cancer (SCLC) patients, to assess the potential relationship between those parameters and to estimate the impact of individual morphological and biological covariates on patients' PK parameters. METHODS: Twenty-four patients with either SCLC limited to the thorax or extensive SCLC entered the study. All but one received at least two 3 day courses of the standard AVI (Dox 50 mg m-2 day 1, Eto 120 mg m-2 day 1,2,3, Ifo 2000 mg m-2 day 1,2) regimen. Individual blood samples were collected during each course and data on 47 courses were available. Data were analysed with the NONMEM program. Dox, Eto and Ifo plasma concentrations were studied with multicompartment (3, 2 and 2, respectively) models. Inter-individual and interoccasion (course-to-course) variabilities were estimated. The influence of individual covariates (age, sex, stage of the disease, weight, height, body-surface area, serum creatinine, total protein, LDH, ASAT, ALAT, alkaline phosphatase, gamma-GT, bilirubin) on PK parameters was also assessed. Correlations between individual PK parameters of Dox, Eto and Ifo were explored by using Pearson's correlation coefficient. RESULTS: Multiple data were available for each patient. Dox clearance (CL) and volume of distribution (Vd) were 32.0 l h-1 and 9.3 l (Inter-individual variability: 17.2% and 19.2%). Eto CL (l h-1) and Vd were, respectively, 3.34-0.0083* serum creatinine (micromol l-1) and 6.38 l (interindividual variability: 15.6% and 18.7%). Ifo CL and Vd at day 1 were 5.6 l h-1 and 26.0 l (interindividual variability: 10.1% and 17.2%, respectively). Estimation of course-to-course variability improved the precision of PK models in some cases. No correlation was observed between the respective PK parameters of each drug. Of individual covariates tested, only serum creatinine correlated with Eto CL (r = -0.37, P < 0.001). Self-induction of the metabolism of Ifo was apparent (mean CL increase from day 1 to day 2 : 42%) and individually correlated with the CL value at day 1 (r = -0.61, P < 0.001). CONCLUSIONS: Assessment of potential relationships between individual systemic exposure of chemotherapy and therapeutic endpoints (tumour response, toxicity and survival) will be required to adjust drugs dosages based on individual PK parameters rather than questionable body-surface area. However, all three drugs in the AVI regimen should be monitored simultaneously.

Aged↗
PubMed2000

Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary.

The aim of this study was to determine the efficacy and toxicity of combination cisplatin and etoposide chemotherapy in patients with metastatic carcinoma of unknown primary. Patients were treated with cisplatin (100 mg/m2 iv day 1) followed by etoposide (100 mg/m2 iv days 1-3) every 3 weeks for a maximum of 6 cycles. Patients with progressive disease after two or four courses could receive FAC (fluorouracil, doxorubicin, and cyclophosphamide) until progression. Twenty-five patients were entered and were assessable for response and toxicity. Fifteen (60%) patients had adenocarcinomas. Patients received a median of four courses. Toxicity was mainly hematologic including grade III/IV neutropenia. The overall response rate was 32%. There was no complete response, 32% partial responses, 32% stable disease, and 36% disease progression. Median response duration was 4 months (range: 2-5 months). The median overall survival of the 25 patients was 8 months. No objective response could be obtained with FAC, but 33% of patients achieved stabilization of the disease for at least 3 months. This cisplatin-etoposide combination demonstrated some activity against an usually resistant disease.

Adenocarcinoma↗
PubMed1999

A sensitive docetaxel assay in plasma by solid-phase extraction and high performance liquid chromatography-UV detection: validation and suitability in phase I clinical trial pharmacokinetics.

We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectivity was obtained through the use of C18 Uptisphere as stationary phase. The low limit of quantitation obtained (LOQ: 5 ng/ml) allowed measurements of docetaxel up to 24 hours after one-hour infusions with low dosages of drug (60 mg/m2). The method was applied successfully to monitor docetaxel plasma levels within two protocols associating fixed dosages of either methotrexate or gemcitabine with escalating doses of Taxotere.

Antimetabolites, Antineoplastic↗
PubMed1999

Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix.

PURPOSE: To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma. PATIENTS AND METHODS: Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (>/= one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field). RESULTS: Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events. CONCLUSION: Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.

Adult↗
PubMed1998

Phase I clinical and pharmacokinetic study of S9788, a new multidrug-resistance reversal agent given alone and in combination with doxorubicin to patients with advanced solid tumors.

PURPOSE: The objectives of this phase I study were to evaluate the toxic effects and the maximum tolerated dose (MTD) of S9788, a new modifier of multidrug resistance (MDR), when given alone and in combination with doxorubicin to patients with advanced solid tumors; to achieve a potentially active plasma concentration of S9788; and to study the pharmacokinetics of both drugs. METHODS: A total of 26 patients (median age 58 years) entered the study. S9788 was given alone as a 30-min infusion at day 1 and in combination with a 50-mg/m2 bolus of doxorubicin at days 8 and 29. Dose levels of S9788 were escalated from 8 to 96 mg/m2 according to the modified Fibonacci scheme. Plasma samples were taken predose as well as during and up to 48 h after the beginning of infusion for S9788 and doxorubicin quantitation. Fractionated urine samples were also collected for up to 24 h for S9788 determination. RESULTS: The dose-limiting side effects of S9788 consisted of bradycardia, sometimes associated with faintness or dizziness. The MTD of S9788 was 96 mg/m2. No enhancement of doxorubicin toxicity was observed. One partial response (duration 140 days) was observed at 96 mg/m2 in a patient with multiple lung metastases from a refractory urothelial carcinoma. Pharmacokinetic studies were performed in 24 patients. Since the mean apparent elimination half-life of S9788 was 46 +/- 23 h and the last plasma sampling time was 48 h, only model-independent parameters were considered. Plasma levels of S9788 were below the limit of quantitation (4 x 10[-3] microM) before each drug administration. S9788 plasma levels of up to 3.7 microM could be obtained with this administration schedule. The urinary elimination of the unchanged drug was negligible, whatever the collection period. In spite of the large inter- and intraindividual variability, plasma pharmacokinetics of S9788 given as a 30-min i.v. infusion were linear up to 96 mg/m2 and were not modified by doxorubicin administration. Doxorubicin pharmacokinetic parameters did not seem to be influenced by S9788 coadministration. CONCLUSION: The dose-limiting toxicity of S9788 consisted of bradycardia or clinical symptoms suggesting a vasovagal impact such as faintness or dizziness. The MTD of S9788 was 96 mg/m2. The pharmacokinetic parameters of doxorubicin in this study were close to those usually described and were not influenced by escalation of the S9788 dose. No pharmacokinetic interaction was observed between S9788 and doxorubicin. The clinical tolerability of the combined treatment is in good agreement with the pharmacokinetic findings, since no enhancement of doxorubicin toxicity was observed.

Adult↗
PubMed1996

Quality of final care for terminal cancer patients in a comprehensive cancer centre from the point of view of patients' families.

The aim of this study was to evaluate the quality of care for terminal cancer patients at our institution, as assessed by families in a questionnaire sent 6 months after the death of the patient. We evaluated the quality of information given to the patients and to their families, the patients' "comfort" at the end of their lives (nursing, pain, psychological support) and the families' opinions about the practical conditions at the time of death (in our institution or at home). A total of 105 consecutive patients who died in our institution between January and June 1989 were included in the study; the vast majority had breast or head and neck cancers. We obtained a total of 48 answers from the 105 families that received the questionnaire. Of these, 87.5% were satisfied with the terminal nursing care, 77% were satisfied with the information given to patients and 60% with the information given to families. The treatment for pain was considered to be inefficient or incomplete by 21% of the families; 32 families (67%) considered that the death of terminal cancer patients should occur in the hospital where the patient had been treated and 12% felt that it should occur at home. This study led us to examine various means for improving the quality of care for our terminal cancer patients.

Adult↗
PubMed1995

[Mucoepidermoid bronchial tumors. General review apropos of 2 new cases].

Muco epidermoïd tumors of the lung are rare tumors, derived from the minor salivary gland tissue of the proximal tracheo bronchial tree. We distinguish high grade and low grade malignity tumors. Authors are presenting two cases reports of mucoepidermoid tumors of the lung with a very aggressive behavior and a review of the literature. Attention is drawn to the difficult differential diagnosis with adenosquamous carcinoma of the lung.

Bronchial Neoplasms↗
PubMed1994

FAC (fluorouracil, doxorubicin, cyclophosphamide) as second line chemotherapy in patients with metastatic breast cancer progressing under FEC (fluorouracil, epirubicin, cyclophosphamide) chemotherapy.

BACKGROUND: The cross-over resistance between different anthracyclines in breast carcinoma has not been largely evaluated in clinical trials. PATIENTS AND METHODS: Nineteen patients with metastatic breast cancer who had failed prior first line FEC chemotherapy (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 cyclophosphamide 500 mg/m2, every 4 weeks) were treated with a combination of fluorouracil 500 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 4 weeks (FAC). RESULTS: Five patients achieved partial responses, ranging in duration from 5 to 8 months. The main toxicity was cardiac, with congestive heart failure documented in five patients. CONCLUSION: The findings indicate an absence of cross resistance of doxorubicin in some epirubicin-resistant patients.

Adult↗
PubMed1994

A phase I antiemetic study of MDL 73,147EF, a novel 5-hydroxytryptamine antagonist in cancer patients receiving emetogenic chemotherapy.

BACKGROUND: We conducted a phase I study with MDL 73,147EF, a new 5 hydroxytryptamine 3 (5-HT3) receptor antagonist, in 25 patients requiring emetogenic chemotherapy. PATIENTS AND METHODS: 5 groups of 5 patients received rising unit doses of MDL 73,147EF (10 to 50 mg) intravenously before chemotherapy, with two additional doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting were recorded by an independent observer. RESULTS: 42% of the patients were complete or major responders on day one. Five patients were given other rescue antiemetic therapy. Adverse effects included headache (16%) diarrhea (8%) and other minor events. The best results were obtained with the 30, 40 and 50 mg doses. CONCLUSIONS: MDL 73,147EF is a well-tolerated and probably effective antiemetic agent which requires further evaluation in randomised controlled clinical studies.

Adult↗
PubMed1993

Phase II study of fotemustine as second-line treatment after failure of immunotherapy in metastatic renal cell carcinoma.

Sixteen patients who after prior systemic immunotherapy had progressing disease received fotemustine (100 mg/m2) i.v. on days 1, 8, and 15 followed by a 5-week rest period. In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 fotemustine given once every 3 weeks until progression on toxicity occurred. No objective response was observed. Four patients showed stable disease (median duration: 4 months; range: 3-19). The main toxicities were neutropenia (WHO grade 3 and 4: 27%) and thrombocytopenia (WHO grade 3 and 4: 27%). Fotemustine was administered on an outpatient basis and was generally well tolerated, but in our series of patients it had no antitumour activity in metastatic renal cell carcinoma after failure of immunotherapy.

Adult↗