Background: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective ...randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. Methods: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan–Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran–Mantel–Haenszel test. All statistical tests were two-sided. Results: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 95% CI = 0.85 to 1.10; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 95% CI = 0.86 to 1.18; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3–4 hematologic toxic effects (requiring more supportive care) and more grade 3–4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm (P = .166). Conclusions: The sequential addition of topotecan to carboplatin–paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.
The aim of this investigation was to assess retrospectively docetaxel safety and efficacy in advanced breast cancer patients in a French compassionate use programme. Patients had received >1 prior ...chemotherapy regimen for advanced disease, were either anthracycline-resistant (that is progressed within 6 months after anthracycline-based chemotherapy) or had received the maximum cumulative dose. The recommended docetaxel dose was 100
mg/m
2/cycle (75
mg/m
2 in case of liver function impairment: transaminases >1.5×upper limit of normal (ULN), alkaline phosphatases >3×ULN). Between August 1993 and December 1995, 889 patients were treated in 67 French centres, of whom 870 were evaluable for safety and 825 were evaluable for patient and treatment characteristics and efficacy. 20.5% (of the 825 patients evaluable for baseline characteristics) had poor performance status (PS≥2), 49.3% liver metastasis and 9.6% biological liver dysfunction. 98.4% had been previously treated by anthracyclines, 50.8% had resistant disease and 37.1% had received >2 prior palliative chemotherapy lines. The most frequent severe toxicity, febrile neutropenia (reported in 223/870 (25.6%) patients evaluable for safety), caused 10 deaths, 6 of these being patients with severe liver impairment before inclusion. Fluid retention syndrome and other common non-haematological toxicities were well tolerated. 3.1% (28/889) of all patients and 11.4% of those with liver dysfunction, died from treatment-related causes. The overall response rate in 825 assessable patients was 22.9% (95% confidence interval (CI): 20.2–26.2%). Median time to treatment failure was 4 months (95% CI: 3.6–4.3) and median survival was 9.8 months (95% CI: 8.8–10.7). This report on the largest series of unselected advanced breast cancer patients treated with docetaxel, supports previous phase II studies, confirming docetaxel's utility in patients relapsing after failing anthracycline-containing palliative chemotherapy.
This phase II study evaluated docetaxel-5-fluorouracil (5-FU) in locally recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Patients were divided into 2 cohorts--those ...previously treated with chemotherapy and those nonpretreated--that received docetaxel 75 mg/m2 (day 1) plus 5-FU 1,000 mg/m2/day (days 1-5 every 3 weeks). Of 63 patients entered, 20 (31.7%) were pretreated and 43 (68.3%) were nonpretreated. Fifty-nine patients (93.7%) had received prior radiotherapy. After inclusion of 20 patients, the 5-FU dose was reduced to 750 mg/m2/day due to unacceptable toxicity. The overall response rate (ORR) was 20.6% on radiologic review (22.2%, investigator assessment). Pretreated patients achieved an ORR of 25.0% versus 18.6% for nonpretreated patients. This unexpected finding was partly attributed to differences in patient characteristics between the groups. Overall major grade 3 to 4 toxicities comprised neutropenia (66.6%), febrile neutropenia (31.7%), and mucositis (31.7%). Grade 3 to 4 toxicities were lower at the reduced 5-FU dose (750 mg/m2/day): Febrile neutropenia declined from 40.0% to 27.9%; mucositis declined from 55.0% to 20.9%. Three treatment-related deaths occurred (2 with 5-FU 750 mg/m2/day, 1 with 5-FU 1,000 mg/m2/day). Docetaxel-5-FU appears active in locally recurrent and/or metastatic SCCHN with acceptable toxicity at the dose of 5-FU 750 mg/m2.
To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas.
Forty-six patients with advanced, histologically ...proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response.
Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis).
Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients.
The “Observatoire des Médicaments et Innovations Thérapeutiques OMIT” directed by ARH Bretagne et Pays de la Loire, has been created in 2002. He’s specialized in oncology, monitoring a few drugs ...every year and brings together public and private hospitals of both two regions on commun objectives. The prescriptions of trastuzumab (Herceptin®) were the object of an analysis in all the establishments listed by OMIT in 2003/2004. Further to the positive results of the trials HERA, NSABP B31 and NCCTG N9831 presented in plenary session to the Congress of the ASCO (Americal Society of Clinical Oncology) in May 2005, and published since, the medical oncologists and the pharmacists of the scientific steering Committee decided to bring together all the data of the patients treated in these situations to know the therapeutic plans used, the incidence of cardiac dysfunction in practice current and their risk factors.
Résumé: L’Observatoire des médicaments et des innovations thérapeutiques (OMIT) Bretagne et Pays de la Loire a été créé en 2003 par lesAgences régionales de l’hospitalisation (ARH) respectives. Il est spécialisé en cancérologie, assure le suivi qualitatif de médicaments en continu et fédère les établissements publics et privés des deux régions sur des objectifs communs. Les prescriptions de trastuzumab (Herceptin®) ont fait l’objet d’une analyse dans tous les établissements recensés par l’OMIT. Suite aux résultats positifs des essais HERA, NSABP B31 et NCCTG N9831 présentés en séance plénière au Congrès de l’ASCO (American Society of Clinical Oncology) en mai 2005, et publiés depuis, les praticiens du comité de pilotage OMIT ont décidé de colliger toutes les données des patientes traitées dans ces situations afin de connaître les schémas thérapeutiques employés, l’incidence des dysfonctionnements cardiaques en pratique courante ainsi que leurs facteurs de risque.
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