Author: RR

Oncoprescribe Blog Anticancer therapy with bisphosphonates

RR

Parenteral therapy with bisphosphonates in patients with skeletal metastases has significantly decreased the risk of skeletal related events and need for radiation therapy. Evolving data suggests that bisphosphonates in general and one of the more commonly used bisphosphonates Zoledronic acid (Zometa) has been shown to induce apoptosis, inhibit angiogensis, inhibit tumor metastases and exhibit synergy with certain anticancer agents in early stage Breast Cancer.

In the Z-FAST and ZO-FAST trials, Zoledronic acid improved disease free survival in hormone receptor positive early stage breast cancer. This intriguing data regarding the benefits of bisphosphonates in early stage breast cancer is likely to move this class of agents into the adjuvant setting, to become a part of adjuvant therapy.

Oncoprescribe Blog Newer agents for hard-to-treat cancers. Sorafenib to the rescue

RR

It was once Renal Cell Carcinoma and then Malignant Melanoma, but now we are about to conquer Hepatocellular carcinoma (HCC). In the SHARP trial published in the NEJM, patients with Hepatocellular carcinoma were randomized to receive either Sorafenib, a raf-kinase inhibitor or placebo. The outcomes were quite striking. Sorafenib significantly improved overall survival with a 31% reduction in the risk of death.

It is important to realize that patients with HCC already have a damaged liver secondary to cirrhosis and the patients in this study predominantly belonged to  Child-Pugh category A .  Sorafenib is presently being studied in combination with Doxorubicin for the treatment of HCC. As we learn more about the pathobiology of a malignancy, drug development to target the molecular mechanism of the disease is becoming a reality.

Oncoprescribe Blog Is Warfarin on its way out?

RR

May be, but not quite. Warfarin is one of the most dangerous oral prescription drugs and is in the top 10 drugs with serious adverse events as has been reported by the  FDA’s Adverse Event Reporting System. The risk of bleeding complications with warfarin is as high as 10%-16%. ( www.archinternmed.com). For this reason FDA has mandated “black box” product warning of bleeding complication for warfarin, in October 2006. Further this drug requires frequent blood monitoring to ensure efficacy and safety. Interaction with other drugs and dietary products is a major drawback of warfarin. First approved for use in the early 1950’s,  warfarin is the most widely prescribed anticoagulant drug in the USA and has remained largely unchallenged until now.

The new players  on the stage are Dabigatran (Pradaxa) and Rivaroxaban (Xarelto). These agents are oral direct thrombin inhibitors. Unlike warfarin, laboratory monitoring is not necessary and drug interactions are uncommon with these agents. The FDA recently approved Dabigatran for stroke prevention in patients with atrial fibrillation. We will soon have these agents also available for the prevention and treatment of Deep Vein Thrombosis (DVT).  This is welcome news for patients on warfarin, who get  stuck at least once a month for laboratory monitoring and have to follow stringent dietary habits to reap the benefits of warfarin.

Oncoprescribe Blog Personalized Therapy based on HPV status in patients with Head and Neck Cancer

RR

Even though long term use of alcohol and tobacco has been implicated as major risk factors for the development of head and neck cancers, it appears that oral HPV (Human Papilloma Virus) 16 accounts for 60% of oropharygeal cancers in the USA. The biology of HPV positive head and neck cancers is different in that it is often seen in younger individuals who do not smoke or drink and tends to originate in the orpharynx and frequently is poorly differentiated with a basaloid nonkeratinizing histopathology. These patients do better that those who are HPV negative.

In an RTOG study, HPV associated oropharynx head and neck cancers responded best to chemoradiation and several retrospective studies have demonstrated a 60% reduction in the risk of death from HPV positive head and neck cancers compared to patients with HPV negative head and neck cancers. Therefore analyzing the tumor for HPV 16 by FISH may be of value in predicting who will benefit best from chemoradiation. In fact ECOG has a study underway evaluating the optimal treatment intervention for HPV positive head and neck cancer patients with the goal of reducing treatment related morbidity but without compromising efficacy.

Armed with this information, we should be able to soon pursue a kinder and gentler approach when treating HPV positive patients with head and neck cancers.

Oncoprescribe Blog More on Romiplostim for ITP

RR

In the November 11, 2010 issue of the NEJM, David Kuter and colleagues reported the results of an open label randomized trial comparing 52 weeks of Romiplostim (Nplate) to “standard of care” in patients with ITP ( Immune Thrombocytopenic Purpura). In this study, Romiplostim was associated with superior platelet response rates, lower rates of treatment failure, improved quality of life and even more importantly, no significantly increased adverse events compared to the standard of care.

In the “Research Regimens”  section at www.oncoprescribe.com, we have a detailed write up on a previous study on Romoplostim by the same author published in Lancet 2008. The Oncoprescribe Blog also has a brief write up on the REMS program.

Romiplostim was approved by the FDA on August 22, 2008 for the treatment of thrombocytopenia in patients with chronic Immune  Thrombocytopenic Purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Armed with the recently published data, it is likely that Romiplostim for ITP could be taking the front row seat.

Oncoprescribe Blog Personalized medicine for prostate cancer patients

RR

Prolaris is a molecular diagnostic tool developed by Myriad Genetics, Inc. This 46 gene panel is capable of predicting  aggressiveness of prostate cancer and can be used in conjunction with Gleason score and PSA. By measuring the  expression level of genes involved with cell cycle progression, this test is able to differentiate indolent from aggressive prostate cancers and therefore predict disease outcome.

In a retrospective analysis of 366 patients who had undergone radical prostatectomy and 337 patients with clinically localized prostate cancer, this gene panel was able to give a favorable and unfavorable score to patient subsets and thus predict clinical outcomes. This prognostic information will allow clinicians to recommend appropriate therapy at the time of diagnosis of prostate cancer.

So we have gene signature assays for breast cancer, colon cancer, lung cancer (oncoprescribe blog) and now for prostate cancer as well. In the end, patients benefit.

Oncoprescribe Blog Abiraterone – another promising agent in CRPC

RR

Abiraterone is a steroidal agent and inhibits CYP17A, an enzyme necessary for the production of androgen precursors and subsequently testosterone. It is capable of inhibiting testosterone production both in the adrenals as well as the testes.

Data from a recent phase III trial was presented at the ESMO meeting and in this International trial involving 1,195 patients, Abiraterone plus a steroid was compared with placebo plus steroid in patients with CRPC (Castrate-Resistant Prostate Cancer) who had failed chemotherapy with Docetaxel. Following an interim analysis and upon recommendation from the Independent Data Monitoring Committeee, the study had to be unblinded, as there was a significant improvement in overall survival in the group receiving Abiraterone. With the availability of several new agents for the treatment of CRPC, it may be important to properly sequence these available drugs to get the best of each treatment intervention and thus improve long term survival with limited toxicity.

Oncoprescribe Blog Cabazitaxel – Another new agent for CRPC

RR

Cabazitaxel is a microtubule inhibitor approved for the treatment of patients with CRPC (Castrate-Resistant Prostate Cancer) who have progressed on Docetaxel. This agent in a randomized phase III trial (TROPIC) demonstrated a significant improvement in Overall Survival (OS) compared with Mitoxantrone, with a 30% reduction in the risk of death. We now have another option for the treatment of CRPC which until not too long back was considered as a disease for which chemotherapy was not effective.

Oncoprescribe Blog CRPC – A wave of new agents, but first Sipuleucel-T

RR

This year 2 new agents have been approved for the treatment of Castrate-Resistant Prostate Cancer – Sipuleucel-T and Cabazitaxel. Sipuleucel-T is composed of autologous antigen-presenting cells (APC’s) from the patient, cultured with a fusion protein PA2024 (Prostate Acid Phosphatase-PAP linked to granulocyte/macrophage colony-stimulating factor). Prostatic Acid Phosphatase (PAP) is an antigen expressed in most prostate cancers. When administered, Sipuleucel-T an autologous active cellular immunotherapy stimulates T cell immunity against PAP and thus the prostate cancer cells. This agent demonstrated improvement in median survival and is best suited for those patients who are asymptomatic or have minimal symptoms with CRPC. It is important to note that this agent is given as three infusions 2 weeks apart and one may not see a drop in the PSA or improvement in the bone scan findings until after three months following treatment. For this reason it is best to consider this agent well before chemotherapy with docetaxel is planned. The number of patients who can be treated with this agent presently is limited due to various barriers associated with the processing of autologous Antigen Presenting Cells. It is important to realize that steroids may counter the T cell response associated with this agent and therefore should be avoided.

Oncoprescribe Blog Predicting Chemotherapy Benefit Using Tumor Gene Expression Signature In NSCLC

RR

A recently published article in JCO is a boost to personalized treatment in Non Small Cell Lung Cancer (NSCLC). A 15-gene expression signature derived from NSCLC tumor was able to predict survival after adjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IB to II NSCLC. This study was done on tumors derived from cohort of patients in the JBR.10 trial where patients received adjuvant cisplatin and vinorelbine. Even though the survival predictability was specific for cisplatin and vinorelbine chemotherapy regimen with this 15-gene signature, one could anticipate the discovery of other tumor mRNA expression signatures for different chemotherapy regimens in the very near future. The ability to predict who will most likely benefit from adjuvant chemotherapy in NSCLC is reminiscent of the developments seen breast and colon cancer.