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CANCER/LEUKEMIA TRIALS ( Last modified 5 NOVEMEBER 2006)
1) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma.J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5.
Summary
PURPOSE: To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients. PATIENTS AND METHODS: Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided. RESULTS: Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone. CONCLUSION: Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.
2) Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphoma. Cancer Sci. 2006 Apr;97(4):305-12
Summary
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.
3) Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis.Lancet Oncol. 2006 Nov;7(11):910-8.
BACKGROUND: Little information is available on how the risk of breast cancer associated with the use of hormone therapy for menopause varies by histological type. We aimed to describe such associations for eight histological types of breast cancer. METHODS: Analyses are based on 1 031 224 postmenopausal women recruited in 1996-2001 into a nationwide UK cohort study, and followed for incident cancer and death. Relative risks associated with use of hormone therapy were estimated for eight histological types of breast cancer. FINDINGS: During 3.6 million person-years of follow-up, 14 102 breast cancers were diagnosed, of which 13 782 (98%) had histological type recorded: 11 869 (86%) were invasive, including 8007 ductal, 1526 lobular, 365 mixed ductal-lobular, 492 tubular, 71 medullary, and 148 mucinous cancers; and 1913 (14%) were in situ, including 1443 ductal and 86 lobular cancers. The relative risks of invasive breast cancer in current users compared with never users of hormone therapy varied significantly according to tumour histology overall (p<0.0001), for users of oestrogen-only therapy (p=0.0001), and for users of oestrogen-progestagen therapy (p<0.0001). The largest relative risks in current compared with never users of hormone therapy were seen for lobular (relative risk 2.25, 95% CI 2.00-2.52), mixed ductal-lobular (2.13, 1.68-2.70), and tubular cancers (2.66, 2.16-3.28). The relative risks for ductal and mucinous cancers were 1.63 (95% CI 1.55-1.72) and 1.58 (1.08-2.31), respectively. The risk of medullary cancer was not increased (0.74, 0.43-1.28). The relative risk of in-situ disease in current users compared with never users of hormone therapy also varied significantly according to histological type (p=0.03), with a relative risk for lobular carcinoma in situ of 2.82 (1.72-4.63) and 1.56 (1.38-1.75) for ductal carcinoma in situ. The effects of hormone therapy on invasive ductal, lobular, and tubular cancer were generally greater for oestrogen-progestagen therapy than for oestrogen-only therapy, and were attenuated with increasing body-mass index (BMI). INTERPRETATION: The risks associated with use of hormone therapy for menopause differ by histological type of breast cancer, and are substantially attenuated with increasing BMI.
4) Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica. 2006 Nov;91(11):1498-505. Epub 2006 Oct 17.
Summary
BACKGROUND AND OBJECTIVES. Induction regimens prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients usually result in complete remission (CR) rates of <10%. The use of novel agents may increase the CR rate before ASCT, which may improve post-transplantation response and survival. DESIGN AND METHODS. This was a phase II, open-label trial of bortezomib (1.3 mg/m(2), days 1,4,8,11) and dexamethasone (40 mg,days 1-4 and 9-12 for cycles 1-2,days 1-4 for cycles 3-4) administered for four 21-day cycles as induction therapy in chemotherapy-naive myeloma patients. RESULTS. Of 52 recruited patients, 48 were eligible for the study. The overall response rate was 66% including 21% CR and 10% very good partial remission (>90% reduction of the M-component). Four patients had a minimal response, six had stable disease and five had progression. One patient died after salvage therapy with VAD. The most common side effects were gastrointestinal symptoms, peripheral neuropathy, and fatigue. These were usually mild. Peripheral neuropathy was observed in 15 cases but was grade 2-3 in only seven cases (14%). There was no deep vein thrombosis and no hematologic toxicity greater than grade 2. Grade 3 infections were recorded in five patients including three who had herpes zoster infections. Stem cell collection was programmed in 44 cases and all patients had sufficient CD34+ cells to perform one ASCT (> 2 x 10(6)/kg). INTERPRETATION AND CONCLUSION. This regimen of bortezomib plus dexamethasone appears effective and well tolerated in newly diagnosed myeloma patients.
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