Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS).
(17/12094)
BACKGROUND: Neoadjuvant chemotherapy improves overall survival and renders possible breast-conserving treatment in locally advanced breast cancer. It was necessary for this method to be evaluated in operable breast tumors too large to be treated immediately by conserving surgery. Initial results of this randomized trial were published in Annals of Oncology (1991). PATIENTS AND METHODS: Women with T2 > 3 cm or T3 N0-1 M0 breast tumors were treated by either initial mastectomy followed by adjuvant chemotherapy, or neoadjuvant chemotherapy followed by adjusted locoregional treatment. Chemotherapy was the same in the two arms. The prognostic and predictive factors of response to chemotherapy were analyzed. RESULTS: Conserving treatments were performed in 63% at the end of neoadjuvant chemotherapy and this rate had decreased to 45% at the median follow-up of 124 months. Survivals are identical in the two treatment groups. Initial clinical tumor size < 40 mm, IHC-ER < 10% and Mib1 > 40% are predictive of tumor response to chemotherapy by uni- and multivariate analyses. For outcome prediction, c-erb-B2 > 0% is the independent prognostic factor for overall and metastasis-free survivals. CONCLUSION: Breast-conserving therapy can be performed in more than half of all cases without alteration of survival, despite a non-negligible rate of local recurrences. (+info)
Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma.
(18/12094)
PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2-4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/microliter to 141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated. (+info)
Reduced health-related quality of life among Hodgkin's disease survivors: a comparative study with general population norms.
(19/12094)
BACKGROUND: Late complications after curative treatment of Hodgkin's disease are of special relevance because most of the cured are young adults. The aims of the present study were: (1) to compare health-related quality of life (HRQOL) in Hodgkin's disease (HD) survivors with normative data from the general Norwegian population and (2) to examine the relations between disease/treatment characteristics and HRQOL in the HD survivors. PATIENTS AND METHODS: 459 HD survivors aged 19-74 years (mean 44.0, SD 11.8) treated at the Norwegian Radium Hospital 1971-1991 were approached in 1994 and compared to norms from 2214 subjects approached in 1996. The norms are representative of the general Norwegian population. HRQOL was assessed by the Short Form 36 (SF-36), which measures HRQOL in eight separate scales (0 = worst health state, 100 = best health state). RESULTS: The HD survivors had lower scores than the normal controls on all scales after adjustment for age, gender and educational levels. Statistically significant differences (P < 0.01) were found in general health (10.4), physical functioning (6.1), role limitations (physical, 9.3), physical functioning (3.6) and in vitality (4.7). Patients with disease stage IB-IIB had the lowest scores on all scales. The differences in relation to stage/substage reached statistical significance (P < 0.01) in physical functioning and in role limitations (physical). Time since diagnosis, types of primary treatment or having relapsed were not associated with statistically significant differences in HRQOL. CONCLUSION: Long-term HD survivors have poorer HRQOL, primarily in physical health, than the general Norwegian population. (+info)
Treatment of mantle-cell lymphomas with intermittent two-hour infusion of cladribine as first-line therapy or in first relapse.
(20/12094)
PURPOSE: Cladribine (2-chlorodeoxyadenosine, 2-CdA) has been reported to be effective in the treatment of low-grade lymphomas. The objective of this multicenter study was to evaluate the activity of cladribine in mantle-cell lymphomas as first-line therapy or in first relapse using an intermittent two-hour infusion of cladribine. PATIENTS AND METHODS: A total of 47 courses, or an average of four courses per patient, were administered to 12 patients (seven untreated, five relapsed) with 5 mg/m2 cladribine given as an intermittent two-hour infusion over five consecutive days for a maximum of six cycles every four weeks. RESULTS: Cladribine showed activity in patients with mantle-cell lymphomas, achieving a response rate of 58% (95% confidence interval (95% CI): 28%-85%). Myelosuppression was the major toxicity with 17% of grade 3 and 4 neutropenia. Thrombocytopenia was rare with only 2% of grade 3 and 4. CONCLUSION: These results demonstrate single-agent activity of cladribine in mantle-cell lymphomas using the intermittent two-hour infusion dosage regimen. To further improve treatment results, cladribine should be combined with other agents active in mantle-cell lymphomas. (+info)
Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group.
(21/12094)
BACKGROUND: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination. PATIENTS AND METHODS: Eligibility criteria included written informed consent, a WHO performance status < 2, life expectancy of > 12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3-antagonists, and corticosteroids. RESULTS: Forty-four patients (median age 55 years, range 35-76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1-6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%-69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses. CONCLUSION: The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck. (+info)
Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel.
(22/12094)
PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P<.001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with non-responders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P<.001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P<.001). CONCLUSION: Forassessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel. (+info)
Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer.
(23/12094)
PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival outcome and incidence of late toxicity for patients with early-stage prostate cancer treated at a single institution with either three-dimensional conformal radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine-125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer, defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score of 6 or lower, and stage less than or equal to T2b, were selected for this analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and 145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64 years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median implant dose was 150 Gy. Prostate-specific antigen relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up times for the 3D-CRT and TPI groups were 36 and 24 months, respectively. RESULTS: Eleven patients (8%) in the 3D-CRT group and 12 patients (8%) in the TPI group developed a biochemical relapse. The 5-year PSA relapse-free survival rates for the 3D-CRT and the TPI groups were 88% and 82%, respectively (P = .09). Protracted grade 2 urinary symptoms were more prevalent among patients treated with TPI compared with 3D-CRT. Grade 2 urinary toxicity, which was manifest after the implant and persisted for more than 1 year after this procedure, was observed in 45 patients (31%) in the TPI group. In these 45 patients, the median duration of grade 2 urinary symptoms was 23 months (range, 12 to 70 months). On the other hand, acute grade 2 urinary symptoms resolved within 4 to 6 weeks after completion of 3D-CRT, and the 5-year actuarial likelihood of late grade 2 urinary toxicity for the 3D-CRT group was only 8%. The 5-year actuarial likelihood of developing a urethral stricture (grade 3 urinary toxicity) for the 3D-CRT and TPI groups was 2% and 12%, respectively (P<.0002). Of 45 patients who developed grade 2 or higher urinary toxicity after TPI, the likelihood of resolution or significant improvement of these symptoms at 36 months from onset was 59%. The 5-year likelihood of grade 2 late rectal toxicity for the 3D-CRT and TPI patients was similar (6% and 11%, respectively; P = .97). No patient in either group developed grade 3 or higher late rectal toxicity. The 5-year likelihood of posttreatment erectile dysfunction among patients who were initially potent before therapy was 43% for the 3D-CRT group and 53% for the TPI group (P = .52). CONCLUSION: Both 3D-CRT and TPI are associated with an excellent PSA outcome for patients with early-stage prostate cancer. Urinary toxicities are more prevalent for the TPI group and subsequently resolve or improve in most patients. In addition to evaluating long-term follow-up, future comparisons will require detailed quality-of-life assessments to further determine the impact of these toxicities on the overall well-being and quality of life of the individual patient. (+info)
Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.
(24/12094)
PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy. (+info)