As we understand the molecular biology of colon cancer, it is becoming clear that tumors with MisMatch Repair Deficiency (MMR-D) and high MicroSatellite Instability (MSI) tend to have a favorable prognosis and do not benefit from chemotherapy and on the contrary, 5-FU based chemotherapy may potentially result in a detrimental effect. The Oncotype DX colon cancer 12 gene assay is a valuable tool that can provide additional information in the decision making process.
Author: RR
Oncoprescribe Blog Malignant Melanoma – An Elusive Disease?
Not anymore. A point mutation in the BRAF proto-oncogene has now been identified. This is detected in approximately 60% of the patients with metastatic melanoma. This mutation appears to be one of the key genetic drivers responsible of the initiation and progression of malignant melanoma. Several selective BRAF inhibitors are in development and these agents have demonstrated significantly high overall response rates. In addition to the anti-CTLA-4 monoclonal antibodies we may soon have a new player with a different mechanism of action to combat this deadly disease.
Oncoprescribe Blog Fulvestrant in Metastatic Breast cancer- New Dosing Schedule
Fulvestrant is a selective estrogen receptor downregulator administered as an injection once a month. Approved in April 2002 by the FDA for the treatment of hormone receptor positive metastatic breast cancer, the recommended dose was Faslodex 250 mg given intramuscularly once a month. FDA has now recommended a new dosing schedule based on the CONFIRM (Comparison of Faslodex in Recurrent or Metastatic Breast Cancer) trial, in which the new dosing schedule significantly prolonged progression free survival compared to the originally recommended dose. The new dosing schedule is as follows – Faslodex 500 mg given intramuscularly on days 1,15 and 29 and monthly thereafter.
Oncoprescribe Blog More progress in Chronic Myeloid Leukemia
Imatinib, a breakthru development in the treatment of CML has been the standard first line treatment for the past several years. This is about to change following presentations at the ASH 2009 and ASCO 2010 meetings.
In the first study Dasatinib was compared head to head with Imatinib in newly diagnosed patients with CML. The complete cytogenetic responses and major molecular responses were higher in the Dasatinib group and these responses were acheived sooner than in the Imatinib group.
In the second study Nilotinib compared to Imatinib in newly diagnosed CML patients resulted in superior complete cytogenetic and major molecular responses.
These second generation BCR-ABL tyrosine kinase inhibitors may take over as first line treatment of CML although economics could play a major role.
Oncoprescribe Blog Another shot at postmenomausal hormone therapy and Breast Cancer
The results of the Women’s Health Initiative (WHI) trial which began in 1993, was updated after a 11 year followup. The outcomes from this study should give us pause as we consider postmenopausal hormonal therapy. The conclusions of this study published in JAMA are clear. Estrogen plus Progestin in postmenopausal women not only increases the risk of breast cancer but also results in more advanced cancer at the time of diagnosis. Further there is an increased rate of breast cancer death in this population. Whether short term use of hormonal treatment in postmenopausal individuals to alleviate symptoms is safe, remains unknown and it may be wise not to consider hormonal treatment in these individuals.
Oncoprescribe Blog Bevacizumab and CNS metastases
The role of Bevacizumab in combination with chemotherapy for patients with advanced Non Small Cell Lung Cancer is well established. However the safety of Bevacizumab in this patient population with brain metastases has been unclear with the potential risk of CNS bleed. This issue was addressed in the PASSPORT trial which enrolled nonsquamous histology Non Small Cell Lung Cancer patients with treated brain metastases. The addition of bevacizumab to conventional chemotherapy or erlotinib in this trial was associated with a low incidence of CNS bleed suggesting that bevacizumab could be safely given for patients with Non Small Cell Lung Cancer with treated brain metastases.
Oncoprescribe Blog Will BRAF trump KRAS testing in Metastatic Colon Cancer?
Testing for KRAS mutations is presently the standard of care prior to treatment with anti EGFR monoclonal antibodies such as cetuximab and panitumumab, as KRAS mutant colorectal tumors do not respond to anti EGFR monoclonal antibodies. However it is becoming clear that BRAF which is involved in intracellular signaling and cell growth and a principal downstream mediator of KRAS, when mutated resulted in shorter progression free survival and overall survival regardless of KRAS status. Targeted therapy may be taking a turn for the better making treatment more personalized.
Oncoprescribe Blog REMS for Romiplostim (Nplate®) and Eltrombopag (PROMACTA®)
The approval of Romiplostim (Nplate®), as well as Eltrombopag (PROMACTA®) included a mandatory Risk Evaluation and Mitigation Strategy (REMS) for the following reasons. There has been some concern raised with regards to long term risks associated with TPO receptor agonists, in particular bone marrow reticulin formation and risk for bone marrow fibrosis. These adverse events however were not noted in the phase III clinical trials. The Risk Evaluation and Mitigation Strategy is intended to ensure that the product is safely used with proper informed consent. It is therefore mandatory that all parties including the prescribers, patients, as well as institutions and pharmacies that wish to provide these drugs, register through the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) program for Romiplostim (Nplate®) and through PROMACTA® CARES for Eltrombopag (PROMACTA®) respectively. These patient registries are meant to monitor long term safety of these agents. REMS will soon be be mandated for ESA’s as well.
Oncoprescribe Blog TCH Adjuvant Therapy for Breast Cancer
BCIRG OO6 – Adjuvant TCH for Breast Cancer presented at the SABCS 2009 by Slamon, D et al. is ready for review.
In summary, here are the findings:
The authors concluded that the addition of trastuzumab to either an anthracycline or non-anthracycline based chemotherapy regimens provides similar and significant benefit both in terms of disease free survival and overall survival and this benefit is seen in both low and high risk patients .
To view the entire Synopsis and Clinical Relevance, log on to https://www.chemoforme.com – if aren’t registered yet; the subscription is free.
Oncoprescribe Blog PROMACTA® (Eltrombopag) for Chronic ITP
The long-term safety and efficacy of (PROMACTA® (Eltrombopag) was evaluated in an open label phase III extension study (EXTEND STUDY) and this study demonstrated that Eltrombopag (PROMACTA®) given for up to two years appears to have consistent benefit in raising the platelet counts without any significant adverse events. A new paradigm has emerged with the availability of a new class of agents such as PROMACTA®, targeting platelet production. Additional trials are underway evaluating the role of this agent in chemotherapy induced thrombocytopenia as well as Myelodysplastic Syndromes and the results are eagerly awaited with renewed interest.