[Show abstract][Hide abstract] ABSTRACT: The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).
Bone Marrow Transplantation 04/2008; 41(6):547-54. DOI:10.1038/sj.bmt.1705925 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Taxane-based chemotherapy has been recently introduced as an effective therapeutic option in recurrent or metastatic endometrial carcinoma (RMEC). The aim of the study was to determine the prognostic factors in RMEC after taxane-based chemotherapy.
One hundred ten patients who received paclitaxel-containing regimen for RMEC were retrospectively evaluated. Potential prognostic factors for overall survival were identified with the Kaplan-Meier method in univariate and the Cox regression model in multivariate analysis.
Performance status (PS) and relapse within the field of previous external radiation were independent prognostic factors for overall survival (p=0.007 and p=0.026 respectively). Non-endometriod histology was associated with a shorter median survival compared to endometriod adenocarcinoma (14.46 vs. 17.57 months, p=0.093), but histology was not an independent prognostic factor (HR=1.43, 95% CI: 0.82-2.48, p=0.21). Stratification according to PS and relapse within the irradiation field identified three risk groups with distinctly different prognosis (median survival 27.36, 16.71, and 11.33 months for the group of favorable, intermediate, and unfavorable prognosis respectively, p<0.001). Within the favorable prognosis group, 34% of patients had a probability of 5-year survival.
PS at diagnosis and relapse within the irradiated area may constitute a valid prognostic model in RMEC patients who receive taxane-based chemotherapy and are able to identify long-term survivors.
[Show abstract][Hide abstract] ABSTRACT: The potential role of the adult thymus in T-cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T-cell pool, a critical process for patients recovering from antineoplastic therapy.
In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow-cytometry, including thymus-derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy.
Adult patients (n = 21, mean age of 30 years, range 18-49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70-91), while total T-cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease-free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T-cell recovery occurred at 6 months post-treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper-naïve) T cells.
The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T-cell pool following chemotherapy-induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naïve repertoire is incomplete.
European Journal of Clinical Investigation 07/2005; 35(6):380-7. DOI:10.1111/j.1365-2362.2005.01499.x · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives. Ifosfamide, paclitaxel, and cisplatin have moderate single-agent activity in patients with metastatic or recurrent cancer of the uterine cervix. We administered a combination of these three agents to a large number of patients with metastatic or recurrent cervical cancer to evaluate its activity. Methods. Sixty patients were treated on an outpatient basis with Ifosfamide (I) 1500 mg/m2 intravenously over 1 h on Days 1–3, paclitaxel (T) 175 mg/m2 as a 3-h intravenous infusion on Day 1, and cisplatin (P) 75 mg/m2 intravenously over 2 h on Day 2 with granulocyte colony-stimulating factor (G-CSF) support. The chemotherapy was repeated every 4 weeks for a maximum of six courses. Results. Fifty-seven patients received at least two courses of treatment and are evaluable for response. Twenty-six patients (46%) achieved an objective response, including 19% complete and 27% partial responses. The median duration of response was 11.5 months and the median time to progression and survival for all patients were 8.3 and 18.6 months, respectively. Patients with excellent performance status, with disease recurrence outside the radiation field, and with nonsquamous tumors had the highest response rate and best survival. Some degree of neurotoxicity occurred in 44% of patients. Grade 3 or 4 toxicity included granulocytopenia in 26% of patients, anemia in 13%, thrombocytopenia in 7%, and neurotoxicity in 3%. Conclusion. The ITP regimen is relatively well tolerated and moderately active in patients with metastatic carcinoma of the uterine cervix. Patients more likely to benefit are those with nonsquamous histology, with excellent performance status, and with disease recurrence outside the radiation field.