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Although an activating mutation of Ras is commonly observed in myelodysplastic syndrome (MDS), the role of Ras in the natural history of MDS remains largely unknown. We prospectively studied efficiency and tolerance of lonafarnib, a compound able to inhibit Ras signalling pathway through an inhibition of farnesyl transferase, in patients with MDS or secondary acute myeloid leukaemia (sAML). Lonafarnib was administered orally at a dose of 200 mg twice daily for three courses of 4 weeks (separated by 1 to 4 weeks without treatment). Sixteen patients were included: FAB/RAEB ( n = 10), RAEB-T ( n = 2), sAML ( n = 2) and chronic myelomonocytic leukaemia (CMML; n = 2); WHO/RAEB-1 ( n = 4), RAEB-2 ( n = 5), AML ( n = 5), CMML ( n = 2). Median age was 70 (53–77) years. The karyotype was complex or intermediate in 11 patients, and the International Prognostic Scoring Systems (IPSS) risk groups were low in two patients, INT-1 in one patient, INT-2 in four patients and high in six patients (unknown or not applicable in three patients). Among the 14 patients tested, five had Ras mutations in codons 12, 13 or 61 of N-Ras, K-Ras or H-Ras. One patient was excluded of the analysis for protocol violation, and 15 patients were assessable for tolerance. Gastrointestinal toxicities (diarrhoea, nausea and anorexia) and myelosuppression were the major side effects. Other toxicities included infections, fatigue, increase of liver enzymes, arrhythmia and skin rash. One patient died of infection, and the treatment was stopped in one other who developed atrial fibrillation. Doses were reduced in all but one patient treated with more than one course of farnesyl transferase inhibitor. Responses were assessable in 12 patients. A partial response in one sAML patient and a very transient decrease of blast cell count with normalisation of karyotype in one MDS patient were observed. No relation between improvement of marrow parameters and detected Ras mutations was observed. Lonafarnib alone, administered following our schedule, has shown limited activity in patients with MDS or secondary AML. Gastrointestinal and haematological toxicities appear the limiting toxicity in this population of patients. [ABSTRACT FROM AUTHOR]

18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) plays an increasing role in the management of patients with lymphoma, for which it is successfully used for staging and treatment monitoring. We report seven patients with a history of lymphoma who presented a positive FDG-PET suggestive of lymphoma relapse and for which FDG-PET oriented biopsies revealed alternative diagnoses. Early in lymphoma follow-up, persistence of focal increased FDG activity corresponded to inflammatory or infectious lesions in two patients: one aspergillosis and one sarcoidosis. Later in the follow-up, five cases of secondary malignancies were identified (three lung cancers, one epidermoid carcinoma, and one villous tumor) in this particularly exposed population. The routine use of FDG PET to evaluate lymphoma significantly increases the probability of detecting unexpected diseases. These cases illustrate the potential pitfalls in PET follow-up. Because FDG is not lymphoma-specific, a relapse suspected only on FDG-PET imaging requires biopsy, as alternative diagnoses--infectious or malignant--are possible. Our data draws clinician's attention to potential false-positive FDG-PET findings, which may lead to therapeutic mistakes. Our data also suggests that FDG-PET might be a new imaging modality for long-term monitoring of late effects, especially second cancer occurrence. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced neutropenia (CIN) places patients at risk of life-threatening infections. While reduction of chemotherapy dose or delay of the subsequent treatment cycle and, consequently, reduction of relative dose intensity (RDI) may limit myelotoxicity, these actions can also impact adversely on treatment outcome and should be avoided in adjuvant settings.Patients and Methods: Based on data from 444 breast cancer patients in the INC-EU Prospective Observational European Neutropenia Study, we have evaluated patient-specific and treatment-specific factors that impact on the incidence of grade 4 CIN (absolute neutrophil count <0.5 × 10(9)/L), either during the first or in any cycle of (neo)adjuvant chemotherapy, across a range of regimens and doses.Results: Using multivariate logistic regression analysis, risk factors for grade 4 CIN were identified as older age, lower weight, higher planned dose intensity of doxorubicin, epirubicin, or docetaxel, higher number of planned cycles, vascular comorbidity, lower baseline white blood cell count, and higher baseline bilirubin. Use of colony-stimulating factor before a neutropenic event occurred, dose delays, and dose reductions were protective against grade 4 CIN.Conclusions: By identifying risk factors for grade 4 CIN, CSF prophylaxis may be appropriately targeted to prevent low RDI in patients treated with curative intent. [ABSTRACT FROM AUTHOR]

Goals Of Work: Neutropenia is a life-threatening, dose-limiting toxicity of many chemotherapy regimens. The goals of this study were to assess the incidence and risk of chemotherapy-induced neutropenia, febrile neutropenia (FN) and dose limitations in breast cancer and lymphoma patients undergoing chemotherapy in Europe.Patients and Methods: Four hundred forty-four breast cancer and 305 lymphoma patients undergoing chemotherapy at 66 practices in five European countries participated in this prospective, observational study. Predictors of impaired chemotherapy delivery were investigated using a logistic regression model.Main Results: In breast cancer, FN incidence was low (6%); however, grade 4 neutropenia was frequent (34%). Lymphoma patients experienced higher incidences of FN (non-Hodgkin lymphoma (NHL) 22%; Hodgkin lymphoma (HL) 15%) and grade 4 neutropenia (NHL 54%; HL 40%). For both diseases, FN and grade 4 neutropenia were associated with low relative dose intensity (RDI). Multivariate regression models indicated that first cycle FN, age > or = 65 years and Eastern Co-operative Oncology Group > 1 were associated with low RDI in breast cancer and lymphoma, while colony-stimulating factor (CSF) primary prophylaxis appeared to be protective in lymphoma only. Primary CSF prophylaxis was provided to 9% of breast cancer, 28% of NHL and 19% of HL patients.Conclusions: Neutropenia and low RDI remain serious problems in both breast cancer and lymphoma populations undergoing chemotherapy. Several risk factors which can trigger reduced chemotherapy delivery were identified. These results can support physicians in identifying patients most at risk of receiving impaired chemotherapy delivery who would benefit from suitable preventive measures. [ABSTRACT FROM AUTHOR]

Introduction: A prospective randomised study involving 810 elderly patients was conducted in an attempt to compare alternating chemotherapy with conventional first-line chemotherapy in aggressive non-Hodgkin’s lymphoma in order to improve prognosis with an acceptable toxicity for elderly patients.Patients and methods: Patients included were 55–69 years old and had at least one adverse prognostic factor. Patients were treated either with ACVBP followed by consolidation (n = 396) or with an alternating regimen (n = 414). This regimen was an association of active drugs in NHL relapsing patients, alternating VIMMM with ACVBP for induction and alternation of VIM and ACVM in consolidation. Eight hundred and sixty-six patients were randomised. After histological review, 810 patients met the inclusion criteria: 396 in arm A, 414 in arm B.Results: The complete response rate after induction was superior for conventional first-line therapy (58.5% vs 48%, P = 0.003) but at the end of treatment, the CR rate was not statistically different (52% vs 48%, P = 0.19). Conventional chemotherapy had a better five-year event-free survival than alternating regimen (33% (95% CI: 30–36%) vs 28% (95% CI: 26–30%), P = 0.0289) but overall survival was not statistically different (40% (CI 95% 38–42%) vs 36% (CI 95% 34–38%), P = 0.068). In this elderly high risk population, the toxicity was very high: 19% in arm A and 26% in arm B died during treatment.Conclusion: Alternating regimen did not improve outcome, was less efficient and more toxic.The Hematology Journal (2001) 2, 279–285 [ABSTRACT FROM AUTHOR]

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)¦ received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m in 60 courses, 300 mg m in 69, 330 mg m in 236 and 350 mg m in 11, with 120 mg m etoposide on days 1, 3 and 5 and either 40 mg m adriamycin or 60 mg m epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m carboplatin had a neutropenia below 200 μ and a thrombopenia below 100,000 μl. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded. This new combination, in which the recommended dose of carboplatin is 330 mg m, should be evaluated in a prospective study for SCLC. [ABSTRACT FROM AUTHOR]