Improved progression-free, but not overall survival with fludarabine plus cyclophosphamide in patients with chronic lymphocytic leukemia
Researchers in the United Kingdom have reported increased progression-free, but not overall survival with fludarabine plus cyclophosphamide in patients with chronic lymphocytic leukemia (CLL), in a study presented in The Lancet this week.
In this study, 777 patients with CLL received fludarabine plus cyclophosphamide, fludarabine alone, or chlorambucil alone. There was no significant difference in overall survival between all three treatments groups. Complete and overall response rates (CR and ORR) were significantly higher with fludarabine plus cyclophosphamide than with fludarabine (CR: 38% vs 15%, respectively; ORR: 94% vs 80%, respectively; p<0•0001), which were significantly higher than with chlorambucil (CR: 7%; ORR: 72%; p=0•006 and 0•04, respectively). Progression-free survival was significantly higher with fludarabine plus cyclophosphamide than with fludarabine or chlorambucil (36% vs 10% vs 10%, respectively; p<0•00005).
A meta-analysis of data from this study and of two other Phase III trials showed a consistent benefit with fludarabine plus cyclophosphamide in terms of progression-free survival.
Author’s conclusions: fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.
Source: http://www.thelancet.com/journals/lancet/article/PIIS0140673607611258/abstract
Sunday, July 22, 2007
Saturday, July 21, 2007
AZD2171 (RECENTIN™) shows promising anti-tumour activity in advanced solid tumours
Researchers have reported that AZD2171 (RECENTIN™; AstraZeneca) shows promising anti-tumour activity and is generally well-tolerated in various advanced solid tumours, in a study reported in the Journal of Clinical Oncology this week.
AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling, thereby inhibiting tumour angiogenesis.
This Phase I study consisted of two parts. In part A, 36 patients with advanced solid tumours and liver metastases received al AZD2171 0.5 to 60 mg, once daily to identify the maximum tolerated dose. In part B, 36 patients with and 11 patients without liver metastases received oral AZD2171 (20, 30 or 45 mg). Patients continued to receive treatment until tumour progression or dose-limiting toxicity occurred.
Eighty-three patients received AZD2171, which was generally well-tolerated up to a dose of 45 mg/day. Most frequently reported adverse events included diarrhea, dysphonia and hypertension, and the most common dose-limiting toxicity was hypertension in 7/83 (8.4%) patients at doses ≥ 20 mg.
Maximum peak drug concentrations after a single dose of AZD2171 occurred between 1 and 8 hours post-AZD2171 administration with a mean half-life of 22 hours.
Promising anti-tumour activity was observed with two (2.4%) patients achieving confirmed partial responses and 22 (26.5) patients achieving stable disease.
Author’s conclusions: Once-daily oral AZD2171 at doses of ≤45 mg was generally well tolerated and associated with encouraging anti-tumour activity in patients with a broad range of advanced solid tumours.
Additional information: a number of clinical trials of AZD2171 as a single-agent or in combination with other agents in various solid tumours are ongoing (follow link below)
http://www.astrazenecaclinicaltrials.com/article/516060.aspx
Source: http://jco.ascopubs.org/cgi/content/abstract/25/21/3045
Researchers have reported that AZD2171 (RECENTIN™; AstraZeneca) shows promising anti-tumour activity and is generally well-tolerated in various advanced solid tumours, in a study reported in the Journal of Clinical Oncology this week.
AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling, thereby inhibiting tumour angiogenesis.
This Phase I study consisted of two parts. In part A, 36 patients with advanced solid tumours and liver metastases received al AZD2171 0.5 to 60 mg, once daily to identify the maximum tolerated dose. In part B, 36 patients with and 11 patients without liver metastases received oral AZD2171 (20, 30 or 45 mg). Patients continued to receive treatment until tumour progression or dose-limiting toxicity occurred.
Eighty-three patients received AZD2171, which was generally well-tolerated up to a dose of 45 mg/day. Most frequently reported adverse events included diarrhea, dysphonia and hypertension, and the most common dose-limiting toxicity was hypertension in 7/83 (8.4%) patients at doses ≥ 20 mg.
Maximum peak drug concentrations after a single dose of AZD2171 occurred between 1 and 8 hours post-AZD2171 administration with a mean half-life of 22 hours.
Promising anti-tumour activity was observed with two (2.4%) patients achieving confirmed partial responses and 22 (26.5) patients achieving stable disease.
Author’s conclusions: Once-daily oral AZD2171 at doses of ≤45 mg was generally well tolerated and associated with encouraging anti-tumour activity in patients with a broad range of advanced solid tumours.
Additional information: a number of clinical trials of AZD2171 as a single-agent or in combination with other agents in various solid tumours are ongoing (follow link below)
http://www.astrazenecaclinicaltrials.com/article/516060.aspx
Source: http://jco.ascopubs.org/cgi/content/abstract/25/21/3045
Wednesday, June 20, 2007
Yttrium-90 ibritumomab tiuxetan is clinically active in patients with advanced diffuse large B-cell lymphoma ineligible for stem-cell transplantation
Researchers have reported that yttrium-90 ibritumomab tiuxetan (Zevalin®; Biogen Idec, Bayer Schering Pharma) has clinical activity in patients with advanced diffuse large B-cell lymphoma who were unable to undergo stem-cell transplantation, in a study reported in the journal Blood this week.
Yttrium-90 ibritumomab tiuxetan is a monoclonal antibody bound via a linker (tiutexan) to the radioisotopes Yttrium-90 or Indium-11, targeting the CD20 antigen on normal and malignant B-lymphocytes. As a result, radiation is directed against CD20 positive cells, inducing cellular damage on the target and neighboring cells.
Yttrium-90 ibritumomab tiuxetan is currently indicated for for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with rituximab-refractory follicular NHL.
In the current Phase II study, elderly patients with first relapsed or primary refractory diffuse large B-cell lymphoma and ineligible for stem-cell transplantation received a single dose of yttrium-90 ibritumomab tiuxetan. Patients had previously been treated with chemotherapy or chemotherapy plus rituximab. Those patients who had previously been treated with chemotherapy were further divided into a) patients in whom induction therapy had failed and b) patients who had relapsed after achieving a complete response.
The overall response rate was higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab (52.5% vs. 19%, respectively). The complete response/complete response unconfirmed rates were higher in patients who had previously received chemotherapy and either failed induction therapy or relapsed after achieving a complete response (24% and 39.5%, respectively) than those patients who had previously been treated with chemotherapy plus rituximab (12%). Median progression free and overall survival were also higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab.
Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Haematologic adverse events were mild to moderate in nature.
Author’s conclusions: ‘Yttrium-90 ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma and its further evaluation in phase 3 studies is ongoing'.
Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/110/1/54
Researchers have reported that yttrium-90 ibritumomab tiuxetan (Zevalin®; Biogen Idec, Bayer Schering Pharma) has clinical activity in patients with advanced diffuse large B-cell lymphoma who were unable to undergo stem-cell transplantation, in a study reported in the journal Blood this week.
Yttrium-90 ibritumomab tiuxetan is a monoclonal antibody bound via a linker (tiutexan) to the radioisotopes Yttrium-90 or Indium-11, targeting the CD20 antigen on normal and malignant B-lymphocytes. As a result, radiation is directed against CD20 positive cells, inducing cellular damage on the target and neighboring cells.
Yttrium-90 ibritumomab tiuxetan is currently indicated for for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with rituximab-refractory follicular NHL.
In the current Phase II study, elderly patients with first relapsed or primary refractory diffuse large B-cell lymphoma and ineligible for stem-cell transplantation received a single dose of yttrium-90 ibritumomab tiuxetan. Patients had previously been treated with chemotherapy or chemotherapy plus rituximab. Those patients who had previously been treated with chemotherapy were further divided into a) patients in whom induction therapy had failed and b) patients who had relapsed after achieving a complete response.
The overall response rate was higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab (52.5% vs. 19%, respectively). The complete response/complete response unconfirmed rates were higher in patients who had previously received chemotherapy and either failed induction therapy or relapsed after achieving a complete response (24% and 39.5%, respectively) than those patients who had previously been treated with chemotherapy plus rituximab (12%). Median progression free and overall survival were also higher in patients who had previously received chemotherapy than those who had previously received chemotherapy plus rituximab.
Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Haematologic adverse events were mild to moderate in nature.
Author’s conclusions: ‘Yttrium-90 ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma and its further evaluation in phase 3 studies is ongoing'.
Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/110/1/54
Tuesday, June 12, 2007
Dasatinib shows promising clinical benefit in patients with chronic myelogenous leukaemia who have failed first-line imatinib
Researchers have reported that the oral dual BCR/ABL and family tyrosine kinase inhibitor, Sprycel® (dasatinib), achieves higher response rates compared with high-dose imatinib, in a Phase II study of patients with imatinib-resistant chronic-phase (CP) chronic myelogenous leukemia (CML), in a study published in the journal Blood this week.
Imatinib, which inhibits the BCR-ABL tyrosine kinase implicated in the pathophysiology of CML, is the therapy of choice for previously untreated chronic-phase CML, achieving complete cytogenetic remission in up to 80% of patients. However, most patients treated with imatinib usually harbor minimal residual disease that eventually leads to disease recurrence.
Dasatinib, is approximately 300 times more potent against BCR-ABL than imatinib, and is currently approved for the second-line treatment of imatinib-resistant CML. In this setting, dasatinib has been shown to induce complete cytogenetic remission in 75% of imatinib-intolerant patients and 40% of imatinib-resistant patients.
In the current study, patients with CP CML resistant to imatinib were randomized to receive 140 mg dasatinib or high-dose imatinib (800 mg). At 15 months, the proportion of patients with a complete haematological response was significantly higher in patients receiving dasatanib versus imatinib (93% vs. 82%, respectively; P = .034), which included complete cytogenetic responses (40% vs. 16%, respectively; P = .004). In addition, the proportion of patients with a major molecular response was significantly higher with dasatinib versus imatinib (16% versus 4%, respectively; P = 0.038). Treatment failure was lower and progression-free survival higher in patients receiving dasatinib versus imatinib (P < .001), although the duration of benefit is not known because of the brief follow-up period.
Superficial oedema and fluid retention were more common in patients receiving imatinib, and pleural effusion was more common with dasatinib. Grade 3 to 4 non-hematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib.
Author’s conclusions: ‘Dasatinib represents a safe and effective therapy for CP CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.’
Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/12/5143
NOTE: A preliminary study presented at ASCO this year suggested that dasatinib mayshow promising clinical benefit as first-line treatment of chronic-phase (CP) chronic myelogenous leukemia (CML) http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=31679
Researchers have reported that the oral dual BCR/ABL and family tyrosine kinase inhibitor, Sprycel® (dasatinib), achieves higher response rates compared with high-dose imatinib, in a Phase II study of patients with imatinib-resistant chronic-phase (CP) chronic myelogenous leukemia (CML), in a study published in the journal Blood this week.
Imatinib, which inhibits the BCR-ABL tyrosine kinase implicated in the pathophysiology of CML, is the therapy of choice for previously untreated chronic-phase CML, achieving complete cytogenetic remission in up to 80% of patients. However, most patients treated with imatinib usually harbor minimal residual disease that eventually leads to disease recurrence.
Dasatinib, is approximately 300 times more potent against BCR-ABL than imatinib, and is currently approved for the second-line treatment of imatinib-resistant CML. In this setting, dasatinib has been shown to induce complete cytogenetic remission in 75% of imatinib-intolerant patients and 40% of imatinib-resistant patients.
In the current study, patients with CP CML resistant to imatinib were randomized to receive 140 mg dasatinib or high-dose imatinib (800 mg). At 15 months, the proportion of patients with a complete haematological response was significantly higher in patients receiving dasatanib versus imatinib (93% vs. 82%, respectively; P = .034), which included complete cytogenetic responses (40% vs. 16%, respectively; P = .004). In addition, the proportion of patients with a major molecular response was significantly higher with dasatinib versus imatinib (16% versus 4%, respectively; P = 0.038). Treatment failure was lower and progression-free survival higher in patients receiving dasatinib versus imatinib (P < .001), although the duration of benefit is not known because of the brief follow-up period.
Superficial oedema and fluid retention were more common in patients receiving imatinib, and pleural effusion was more common with dasatinib. Grade 3 to 4 non-hematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib.
Author’s conclusions: ‘Dasatinib represents a safe and effective therapy for CP CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.’
Source: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/109/12/5143
NOTE: A preliminary study presented at ASCO this year suggested that dasatinib mayshow promising clinical benefit as first-line treatment of chronic-phase (CP) chronic myelogenous leukemia (CML) http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abstractID=31679
Saturday, June 09, 2007
A healthy lifestyle may improve survival after breast cancer diagnosis
American researchers have reported that physically active women who eat a high vegetable and fruit diet have improved survival regardless of obesity according to a study published this week in the Journal of Clinical Oncology.
The authors of this study followed about 1,500 women diagnosed and treated for early-stage breast cancer. The combination of eating ≥5 daily servings of vegetables and fruits plus taking regular exercise equivalent to walking 30 minutes/day per week was associated with a 44% increase in survival. In addition, there was no apparent effect of obesity on survival.
Author’s conclusions: A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables and fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.
Source: http://jco.ascopubs.org/cgi/content/abstract/25/17/2345
American researchers have reported that physically active women who eat a high vegetable and fruit diet have improved survival regardless of obesity according to a study published this week in the Journal of Clinical Oncology.
The authors of this study followed about 1,500 women diagnosed and treated for early-stage breast cancer. The combination of eating ≥5 daily servings of vegetables and fruits plus taking regular exercise equivalent to walking 30 minutes/day per week was associated with a 44% increase in survival. In addition, there was no apparent effect of obesity on survival.
Author’s conclusions: A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables and fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.
Source: http://jco.ascopubs.org/cgi/content/abstract/25/17/2345
Thursday, June 07, 2007
Cisplatin superior to carboplatin for first-line treatment of non-small-cell lung cancer
Researchers have reported a higher response rate for cisplatin compared with carboplatin when used to treat non-small cell lung cancer (NSCLC) according to results presented in this month’s Journal of the National Cancer Institute.
Pooled data from nine clinical trials comparing cisplatin to carboplatin as first-line treatment of patients with stage IIIb-IV non-small-cell lung cancer were analysed. The author’s found a significantly higher objective response rate (ORR) with cisplatin versus carboplatin (30% versus 24%, respectively; P<.001). There was a trend towards increased survival in patients receiving cisplatin, compared with those patients receiving carboplatin. In addition, cisplatin was more effective in prolonging survival in cases treated with third-generation regimens and in those with non-squamous histology.
Author’s conclusions: ‘Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity, wherease severe thrombocytopenia was more frequent during carboplatin-based chemotherapy.
Source: http://jnci.oxfordjournals.org/cgi/content/abstract/99/11/847
Researchers have reported a higher response rate for cisplatin compared with carboplatin when used to treat non-small cell lung cancer (NSCLC) according to results presented in this month’s Journal of the National Cancer Institute.
Pooled data from nine clinical trials comparing cisplatin to carboplatin as first-line treatment of patients with stage IIIb-IV non-small-cell lung cancer were analysed. The author’s found a significantly higher objective response rate (ORR) with cisplatin versus carboplatin (30% versus 24%, respectively; P<.001). There was a trend towards increased survival in patients receiving cisplatin, compared with those patients receiving carboplatin. In addition, cisplatin was more effective in prolonging survival in cases treated with third-generation regimens and in those with non-squamous histology.
Author’s conclusions: ‘Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity, wherease severe thrombocytopenia was more frequent during carboplatin-based chemotherapy.
Source: http://jnci.oxfordjournals.org/cgi/content/abstract/99/11/847
Wednesday, June 06, 2007
Increased coffee consumption may reduce the risk of liver cancer
Swedish researchers have reported that an increase in consumption of 2 cups of
coffee per day is associated with a reduced risk of liver cancer, in a study reported in May’s issue of the journal Gastroenterology.
The authors, Drs Susanna Larsson and Alicja Wolk, pooled data in a meta-analysis of nine clinical studies (5 cohort and 4 case-control studies) involving 2,260 cases and 239,146 non-cases.
They found an inverse association between coffee consumption and risk of liver cancer that was statistically significant in 6/9 studies. The authors reported that an increase in coffee consumption of 2 cups per day was association with 43% reduction in risk of liver cancer.
The authors note several lines of evidence that a protective effect of coffee consumption on liver is biologically plausible. For example, coffee contains antioxidants such as chlorogenic acids, and animal studies have shown an inhibitory effect of coffee and chlorogenic acids on liver cancer
Author’s conclusions ‘Findings from this meta-analysis indicate
that coffee consumption may reduce the risk of liver cancer. The mechanisms involved and the substances in coffee that may be responsible for the relation remain to be elucidated.’
Source: http://www.gastrojournal.org/article/PIIS0016508507005689/abstract
Swedish researchers have reported that an increase in consumption of 2 cups of
coffee per day is associated with a reduced risk of liver cancer, in a study reported in May’s issue of the journal Gastroenterology.
The authors, Drs Susanna Larsson and Alicja Wolk, pooled data in a meta-analysis of nine clinical studies (5 cohort and 4 case-control studies) involving 2,260 cases and 239,146 non-cases.
They found an inverse association between coffee consumption and risk of liver cancer that was statistically significant in 6/9 studies. The authors reported that an increase in coffee consumption of 2 cups per day was association with 43% reduction in risk of liver cancer.
The authors note several lines of evidence that a protective effect of coffee consumption on liver is biologically plausible. For example, coffee contains antioxidants such as chlorogenic acids, and animal studies have shown an inhibitory effect of coffee and chlorogenic acids on liver cancer
Author’s conclusions ‘Findings from this meta-analysis indicate
that coffee consumption may reduce the risk of liver cancer. The mechanisms involved and the substances in coffee that may be responsible for the relation remain to be elucidated.’
Source: http://www.gastrojournal.org/article/PIIS0016508507005689/abstract
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