Therapy of advanced lymphocytic lymphoma a preliminary report of a randomized trial between combination chemotherapy (CVP) and intensive radiotherapy.
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The initial results of a randomized clinical trial comparing intensive cyclical combination chemotherapy (CVP) and total body radiation therapy in the treatment of advanced (Stage III and IV) lymphocytic lymphoma is presented. Sixty-five patients have been entered and randomized according to stage. Of the chemotherapy treated patients, (22/27 (81%) achieved a response with 55% complete responders. The radiation group or those treated with radiation 27/32 (84%) responded with 56% in complete response. There is no significant difference in overall survival between the two groups. Nodular lymphoma (44 patients) responds more often and has s significantly longer survival than diffuse lymphoma (21 patients). Approximately 50% of the complete remitters have relapsed but reinduction of disease control was possible in almost all cases. (+info)
Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever.
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The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance. (+info)
Phase I dose-finding study of a new taxane, RPR 109881A, administered as a one-hour intravenous infusion days 1 and 8 to patients with advanced solid tumors.
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PURPOSE: To define the maximum-tolerated dose, recommended phase II dose (RD), dose-limiting toxicity (DLT), and pharmacokinetics of a novel taxane, RPR 109881A, administered on days 1 and 8 of a 21-day cycle. PATIENTS AND METHODS: Twenty-nine patients were enrolled and treated according to a modified continual reassessment method from a starting dose of 7.5 mg/m(2) to 52.5 mg/m(2). Detailed pharmacokinetic analyses of blood and urine were performed on days 1 and 8 of the first cycle. Toxicity was monitored weekly. RESULTS: DLT consisting of grade 3 or 4 diarrhea was seen in three of six patients at 52.5 mg/m(2). Grade 3 or 4 granulocytopenia was also seen in five of six patients treated at this dose (four of six in the first cycle). At the next lower dose level, 45 mg/m(2) toxicity was moderate, with only one of 12 patients experiencing severe diarrhea and grade 4 granulocytopenia with associated infection. Drug concentrations were consistent with a three-compartment open model. The total-body clearance suggests a linear dose-concentration relationship. RPR 109881A has a high clearance (mean, 42.6 L/h/m(2)), a large volume of distribution (mean, 952 L/m(2)), and a long terminal half-life (mean, 24 hours). There was no drug accumulation between days 1 and 8. One partial response was seen in a patient with renal cell carcinoma. CONCLUSION: The RD of RPR 109881A given as a 1-hour infusion on days 1 and 8 of a 21-day cycle is 45 mg/m(2). At this dose the drug is well tolerated and should be further studied. (+info)
Depression of bone marrow colony formation in gold-induced neutropenia.
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Bone marrow culture in semi-solid agar was used to assess the proliferative activity and the response to sodium aurothiomalate of the myeloid precursor cells from patients during and after recovery from neutropenia associated with the use of this drug. Colony formation was reduced during the neutropenia and returned to normal after recovery. The rheumatoid process itself did not impair colony formation even in patients with Felty's syndrome. Sodium aurothiomalate inhibited colony formation by normal marrow in a dose-dependent manner. Bone marrow colonies from patients who had recovered from neutropenia induced by sodium aurothiomalate were not abnormally sensitive to the inhibitory effect of the drug in vitro. The metabolism of gold is probably altered in a small proportion of patients, which causes high local concentrations within the bone marrow leading directly to marrow depression. (+info)
Randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients.
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In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients. (+info)
Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393.
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PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended. (+info)
Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog.
(31/458)
PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors. PATIENTS AND METHODS: Twenty-two patients with advanced solid tumors, all previously treated, and with performance status < or = 2, were entered. The starting dose of DX-8951f was 0.15 mg/m(2); the dose was escalated according to the modified continual reassessment method. The drug was administered until disease progression or until unacceptable toxic effects occurred. RESULTS: Seven dose escalations were completed, and a total of 53 courses were delivered (median, two courses; range, one to eight courses) during the study. At doses 1.2 mg/m(2) and lower, toxicities were mostly grade 1, primarily hematologic. In the initial cohort of three patients treated at 2.4 mg/m(2), grade 2 hematologic toxicity was observed. Of the six additional patients entered at 2.4 mg/m(2), three had grade 3 or 4 granulocytopenia. At doses higher than 2.4 mg/m(2), DLT granulocytopenia was observed. Nonhematologic toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were mild to moderate. Neither complete nor partial responses were observed, but four patients had stable disease. The PK profile of DX-8951f seemed linear at the doses administered. The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively. CONCLUSION: The DLT of this DX-8951f schedule was granulocytopenia for minimally pretreated patients, and both granulocytopenia and thrombocytopenia for heavily pretreated patients. The MTD for both minimally and heavily pretreated patients was 2.4 mg/m(2). DX-8951f seems to have a linear PK profile on the basis of single-dose administration. The recommended phase II dose with this schedule is 2.4 mg/m(2) for minimally pretreated patients. A lower dose should be used for heavily pretreated patients. (+info)
Risk factors for anaerobic bloodstream infections in bone marrow transplant recipients.
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The incidence of anaerobic bloodstream infections (BSI) in patients who underwent bone marrow transplantation (BMT) recently increased at our institution. A retrospective case-control study of patients undergoing BMT from January 1995 through December 1998 was performed to determine the microbiological characteristics, epidemiology, and outcome of anaerobic BSI and to identify independent risk factors for infection. Anaerobic BSI occurred in 23 patients, for a rate of 4 BSIs per 100 BMT procedures, and it accounted for 17% of all BSIs that occurred during the study period. Infection occurred at a mean (+/- standard deviation) of 7+/-4 days after BMT and 7+/-5 days after the onset of neutropenia. Fusobacterium nucleatum was the most frequently isolated pathogen (in 17 patients), followed by Leptotrichia buccalis (in 4), Clostridium septicum (in 1), and Clostridium tertium (in 1). Two case patients (9%) died. Severity of mucositis was an independent predictor of anaerobic BSI (odds ratio, 4.4; P=.01). Controlling mucositis is critical for the prevention of anaerobic BSI in this patient population. (+info)