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Non-hematological Toxicities (non-hematological + toxicity)
Selected AbstractsToxicity of docetaxel plus cyclophosphamide as adjuvant therapy for breast cancer in Chinese patients , the Hong Kong experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Tsz-Kok YAU Abstract Aims: The docetaxel and cyclophosphamide (TC) regimen is increasingly popular as adjuvant chemotherapy for operable breast cancers. We conducted a retrospective study in Hong Kong to evaluate the toxicity of this regimen in Chinese patients. Methods: Between January 2007 and May 2008 76 female Chinese patients with resected stage I,III operated invasive breast cancer were treated with 4 cycles of TC (75 and 600 mg/m2, respectively, administered i.v. every 3 weeks for four cycles) in two public regional cancer centers of Hong Kong. A total of 24 (32%) patients also received primary prophylactic ciprofloxacin (500 mg twice daily, day 5,14). Chemotherapy-related toxicities were graded by the CTCAE version 3.0. Results: The median age was 50 (range 26,67). A total of 68 (89%) patients successfully completed four cycles of chemotherapy. 72 (95%) and 16 (21%) patients developed grade 3,4 neutropenia and febrile neutropenia (FN) infection, respectively, in one or more cycles. However, no grade 3,4 anemia or thrombocytopenia events were observed. Other grade 3,4 non-hematological toxicities were also uncommon, apart from allergic reactions in two (3%) patients. No viral reactivation was observed among the 8 hepatitis B carriers. Patients with prophylactic ciprofloxacin had less grade 3,4 FN infection (13% vs 25%, P = 0.214) and a higher chance of receiving the full scheduled dose (88% vs 62%, P = 0.045) than patients without. Conclusion: The myelotoxicity of TC was substantially higher in Chinese patients compared with non-Chinese patients in developed countries. Routine prophylactic measures are recommended to maintain the dose levels and reduce the risk of FN. [source] Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non-small-cell lung cancer: Is thrombocytopenia predictable?ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Cathy CROMBIE Abstract Aim: Two 21-day gemcitabine,carboplatin schedules were evaluated in patients with advanced non-small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy. Methods: Patients were randomized to gemcitabine (1000 mg/m2 on days 1 and 8 of a 21-day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non-small-cell lung cancer were enrolled in each arm. Results: The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non-hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13,41%). Conclusion: Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed. [source] Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphomaCANCER SCIENCE, Issue 4 2006Michinori Ogura CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n = 34) or sequential (n = 35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85,100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation. (Cancer Sci 2006; 97: 305 , 312) [source] Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOPEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2002A Hellenic Co-operative Oncology Group Study Abstract:Introduction: During the last few years epirubicin (E) and mitoxantrone (M) (Novantrone) have been used in the treatment of non-Hodgkin's lymphoma (NHL), because of their favorable principal profile. In particular, M has less severe non-hematological toxicity. Patients and methods: A randomized multicenter phase III study was conducted in order to compare the efficacy and toxicity of CEOP and CNOP in intermediate- and high-grade NHL. CEOP (arm A) consisted of cyclophosphamide 1000 mg m,2, vincristine 2 mg, E 70 mg m,2 on day 1 and prednisone 60 mg on days 1,7. The CNOP regimen (arm B) was identical to CEOP except for replacement of E by M at a dose of 12 mg m,2. Randomization was stratified according to stages I,IV. From September 1993 to March 1999, 249 patients registered for the trial. Patient characteristics were equally distributed in the two arms, except for age and International Prognostic Index (IPI) groups. Results: There were no significant differences between the two groups in the rates of complete (CR) and partial response (PR). The overall response rate was 78% in arm A (57% CR, 21% PR) and 82% in arm B (60% CR, 22% PR). With a median follow-up time of 47.3 months, the median survival was not reached in arm A, while it was 39.5 months in arm B (P = 0.09). Three-year survival rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference regarding the time to progression between the two groups (29.7 vs. 18.5 months); furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP, respectively (P = 0.07). The therapeutic efficacies of both regimens were equivalent among the four IPI groups. More alopecia was observed in arm A. WHO grade >2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF was given to 22 and 24 patients, respectively. Conclusion: There were no significant differences in terms of overall response rates, overall survival and time to progression between CEOP and CNOP in the treatment of intermediate- and high-grade NHL. Patients with low or low intermediate IPI risk treated with either CEOP or CNOP showed significantly better survival, response rates and time to progression than those with high intermediate or high IPI risk. Therefore, new improved therapeutic approaches should be developed for the treatment of high IPI risk patients. [source] Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high-dose melphalan and total body irradiation preparative for bone marrow transplantation in childrenPEDIATRIC TRANSPLANTATION, Issue 4 2000K. Vettenranta Abstract: The use of high-dose melphalan ( l -phenyalalanine mustard or l -PAM) has been shown to be associated with both hematological and non-hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high-dose l -PAM (210 mg/m2) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high-dose l -PAM experienced a markedly more severe acute graft-vs.-host disease (GvHD). The overall incidence of grade III,IV acute GvHD was higher (86% vs. 14%) among those treated with l -PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages ++ to ++++) gut GvHD was strikingly more prevalent among those treated with l -PAM (86% vs. 9%, p<0.005). Toxic mortality prior to day +100 was 29% in the l -PAM group and 9% in the non- l -PAM group of patients. With a mean follow-up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with l -PAM. We conclude that the use of preparative L -PAM for allogeneic transplants from unrelated donors is associated with considerable procedure-related toxicity. We strongly suggest its use in this setting to be viewed with caution. [source] Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeksCANCER SCIENCE, Issue 2 2009Nobuyuki Yamamoto TZT-1027 is a novel synthetic dolastatin 10 derivative that inhibits tubulin polymerization. A phase I study was conducted to determine the maximum tolerated dose (MTD) of TZT-1027, and to assess its pharmacokinetic profile in Japanese patients with advanced solid tumors following administration of the drug weekly for 3 weeks. Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, and met the following criteria: performance status ,2 and acceptable organ function. The MTD was defined as the highest dose at which more than two-thirds of the patients experienced grade 4 hematological toxicity or grade 3/4 non-hematological toxicity during weekly TZT-1027 administration for 3 weeks. Forty patients were enrolled in the present study. Twelve doses between 0.3 and 2.1 mg/m2 were evaluated. Grade 4 neutropenia was the principal dose-limiting toxicity (DLT). At a dose of 2.1 mg/m2, two patients developed DLT: one patient developed grade 4 neutropenia, grade 3 myalgia, and grade 4 constipation, and the other one developed grade 4 neutropenia and grade 3 constipation. At a dose level of 1.8 mg/m2, toxicity was acceptable and no DLT was observed. The area under the curve and maximum concentration of TZT-1027 tended to increase linearly with the dose. The DLT observed were neutropenia, myalgia, and constipation, and the MTD was 2.1 mg/m2. The recommended dose for a phase II study was determined to be 1.8 mg/m2 for the drug administered weekly for 3 weeks. (Cancer Sci 2009; 100: 316,321) [source] | ||||||||||