Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma.
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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)
Is primary CNS lymphoma really becoming more common? A population-based study of incidence, clinicopathological features and outcomes in Alberta from 1975 to 1996.
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BACKGROUND: The incidence of primary CNS lymphoma (PCNSL) is believed to be increasing in immunocompetent patients but this may not be universally true. The objective of this study was to determine in a population if the incidence of PCNSL is increasing, if the histologic subtypes are changing, and to describe the clinicopathologic and outcome characteristics of PCNSL. PATIENTS AND METHODS: We identified all Alberta residents with a histologic diagnosis of PCNSL from 1 January 1975 to 31 December 1996 using the Alberta Cancer Registry. Annual age-standardized incidence rates (ASIR), clinicopathologic and outcome characteristics were determined. RESULTS: There were 50 immunocompetent PCNSL patients; the median age was 64 and 30 were male. Their median survival was 10.15 months. Histology was available for review in 37 (74%) patients: 19 (51%) were diffuse large cell, 16 (43%) were immunoblastic and 2 (5%) were unclassifiable malignant lymphomas. The ASIR ranged from 0.178-1.631/10(6) and no change in ASIR was found (test for trend, P = 0.26) for gender or age. The ASIR of malignant gliomas did not change either but increased for all other non-Hodgkin's lymphoma (94.95-138.7610(6); test for trend, P = 0.0001) The number of brain biopsies increased from 1979-1985 (test for trend, P < 0.0001) but remained stable from 1986-1996 (test for trend, P = 0.99). CONCLUSIONS: Unlike several other populations, PCNSL is not becoming significantly more common in Alberta. If this difference is real (i.e., not due to differences in cancer registry coding practices etc.) comparisons between Albertans and other populations in whom the incidence is rising may provide clues regarding the etiology of PCNSL. (+info)
Treatment of mantle-cell lymphomas with intermittent two-hour infusion of cladribine as first-line therapy or in first relapse.
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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.
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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)
Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer.
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OBJECTIVE: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer. METHODS: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination. RESULTS: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease. (+info)
Reexploration for periampullary carcinoma: resectability, perioperative results, pathology, and long-term outcome.
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OBJECTIVE: This single-institution experience retrospectively reviews the outcomes of patients undergoing reexploration for periampullary carcinoma at a high-volume center. SUMMARY BACKGROUND DATA: Many patients are referred to tertiary centers with periampullary carcinoma after their tumors were deemed unresectable at previous laparotomy. In carefully selected patients, tumor resection is often possible; however, the perioperative results and long-term outcome have not been well defined. METHODS: From November 1991 through December 1997, 78 patients who underwent previous exploratory laparotomy and/or palliative surgery for suspected periampullary carcinoma underwent reexploration. The operative outcome, resectability rate, pathology, and long-term survival rate were compared with 690 concurrent patients who had not undergone previous exploratory surgery. RESULTS: Fifty-two of the 78 patients (67%) undergoing reexploration underwent successful resection by pancreaticoduodenectomy; the remaining 26 patients (34%) were deemed to have unresectable disease. Compared with the 690 patients who had not undergone recent related surgery, the patients in the reoperative group were similar with respect to gender, race, and resectability rate but were significantly younger. The distribution of periampullary cancers by site in the reoperative group undergoing pancreaticoduodenectomy (n = 52) was 60%, 19%, 15%, and 6% for pancreatic, ampullary, distal bile duct, and duodenal tumors, respectively. These figures were similar to the 65%, 14%, 16% and 5% for resectable periampullary cancers found in the primary surgery group (n = 460). Intraoperative blood loss and transfusion requirements did not differ between the two groups. However, the mean operative time was 7.4 hours in the reoperative group, significantly longer than in the control group. On pathologic examination, reoperative patients had smaller tumors, and the percentage of patients with positive lymph nodes in the resection specimen was significantly less. The incidence of positive margins was similar between the two groups. Postoperative lengths of stay, complication rates, and perioperative mortality rates were not higher in reoperative patients. The long-term survival rate was similar between the two resected groups, with a median survival of 24 months in the reoperative group and 20 months in those without previous exploration. CONCLUSIONS: These data demonstrate that patients undergoing reoperation for periampullary carcinoma have similar resectability, perioperative morbidity and mortality, and long-term survival rates as patients undergoing initial exploration. The results suggest that selected patients considered to have unresectable disease at previous surgery should undergo restaging and reexploration at specialized high-volume centers. (+info)
Ten-year trend in survival and resource utilization at a level I trauma center.
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OBJECTIVE: To determine the impact of increasing trauma center experience over time on survival and resource utilization. METHODS: The authors studied a retrospective cohort at a single level I trauma center over a 10-year period, from 1986 to 1995. Patients included all hospital admissions and emergency department deaths. The main outcome measures were the case-fatality rate adjusted for injury severity, hospital length of stay, and costs. RESULTS: A total of 25,979 patients were admitted or died. The number of patients per year increased, from 2063 in 1986 to 3313 in 1995. The proportion of patients transferred from another institution increased from 16.2% to 34.4%. Although mean length of stay declined by 28.4%, from 9.5 to 6.8 days, costs increased by 16.7%, from $14,174 to $16,547. The use of specific radiologic investigations increased; the frequency of operative procedures either remained unchanged (craniotomy, fracture fixation) or decreased (celiotomy). After adjusting for injury severity and demographic factors, the mortality rate decreased over 10 years. The improvement in survival was confined to patients with an injury severity score > or =16. CONCLUSION: Over a 10-year period, the case-fatality rate declined in patients with severe injuries. Overall acute care costs increased, partially because of the increased use of radiologic investigations. Even in otherwise established trauma centers, increasing cumulative experience results in improved survival rates in the most severely injured patients. These data suggest that experience contributes to a decrease in mortality rate after severe trauma and that developing trauma systems should consider this factor and limit the number of designated centers to maximize cumulative experience at individual centers. (+info)
Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials.
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Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI). BACKGROUND: Trials in post-MI patients have shown that ACE inhibitor therapy reduces mortality. However, the effect on SCD as a mechanism has not been clarified. METHODS: Trials of ACE inhibitor therapy following MI reported between January, 1978 and August, 1997 were identified. Studies were included if they met the following criteria: 1) randomized comparison of ACE inhibitor to placebo within 14 days of MI; 2) study duration/blinded follow-up of > or =6 weeks; 3) the number of deaths and modes of death were reported or could be obtained from the investigators. RESULTS: We identified 374 candidate articles, of which 15 met the inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died. Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant reduction in SCD risk or a trend towards this was observed in all of the larger (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant reductions in risk of death (random effects odds ratio [OR] = 0.83; 95% confidence interval [CI] 0.71-0.97), cardiovascular death (OR = 0.82; 95% CI 0.69-0.97) and SCD (OR = 0.80; 95% CI 0.70-0.92). CONCLUSIONS: This analysis is consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality. Moreover, this analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit. (+info)