Cancer Treatment

Sprycel for melanoma

Dasatinib, also known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is a promising drug for melanoma and the clinicaltrials.gov websit lists 4 ongoing phase II trials, for example, Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma, NCT00436605. Melanomas from acral lentiginous, mucosal and chronic sun-damaged sites frequently harbor activating mutations and/or increased copy number in the KIT tyrosine kinase receptor gene, which are very rare in more common cutaneous melanomas. Multiple case reports and early observations from clinical trials suggested that targeting mutant KIT with small molecule KIT inhibitors such as imatinib (Gleevec, Novartis) and/or dasatinib (Sprycel, BristolMyersSquibb) is efficacious. Unfortunately, I was not able to find any published trial evidence to support the clincal use of dasatinib(Sprycel) for mealnoma at the current time.

nccn.org, melanoma

Wen-Jen Hwu, MD, PhD, HemOnc Today, Targeted therapy for metastatic melanoma: From bench to bedside  June 25, 2010

Target Now

Caris Life Sciences'™ molecular profiling test, Caris Target Now®, examines the genetic and molecular changes of a patient's tumor so that treatment options may be matched to the tumor's molecular profile.

Caris Target Now purports to help treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor's information with data from published clinical studies by thousands of the world's leading cancer researchers, Caris claims to be able to help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

This approach represents a cutting edge of diagnostic science, sometimes termed, "Personalized Medciine". The concept that one can individualize cancer therapy based on specific tumor characteristics is attractive but needs to be proven before being widely adapted. As of now, there is little evidence to support it and no guidelines or professional bodies recommending it.

Caris writes on its website: "Our evidence team has reviewed more than 60,000 clinical literature manuscripts that support associations between biomarkers and treatments.  The Caris Target Now database is continually updated with the latest research and emerging biomarker information.

This ongoing process ensures that only the most relevant and appropriate tests are included in the Caris Target Now panel. Better information can lead to better decisions. Better decisions can lead to better health outcomes."

This processand  information remains proprietary and not peer-reviewed.

Daniel D. Von Hoff et al, Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers JCO October 4, 2010

Burstein HJ.Personalized medicine and breast cancer care.

J Natl Compr Canc Netw. 2009 Feb;7(2):109.

 

Companion Diagnostics in Personalized Medicine and Cancer Therapy

Trimark Publications (190 pages), published Apr 2008

Bendamustine, Mitozantrone and Rituxan for lymphoma

The concept fo cmbining bendmustine, mitozantrone and Rituxan is based on German reports of high activity of this regimen in follicular and mantle cell lymphomas. However, these results require confirmation and there are no guidelines that recommend this combination. A 2009 review condluded: "Overall, bendamustine has demonstrated promising results as therapy for non-Hodgkin's lymphomas and should be included in the armamentarium of agents used to treat relapsed indolent non-Hodgkin's lymphomas and may prove valuable as initial therapy for these diseases. Further studies are being conducted to demonstrate the efficacy of this drug in combination with other agents."
In addition, the combination is in a study: Bendamustine, Mitoxantrone, and Rituximab (BMR) for Patients With Untreated High Risk Follicular Lymphoma, NCT00901927

Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, Aldaoud A, Losem C, Schmitz S, Haak U, Huber C, Unterhalt M, Hiddemann W, Dreyling M; German Low Grade Lymphoma Study Group.
High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma. 2007 Jul;48(7):1299-306.

V. Gandhi and J. A. Burger
Bendamustine in B-Cell Malignancies: The New 46-Year-Old Kid on the Block
Clin. Cancer Res., December 15, 2009; 15(24): 7456 - 7461.

Dacogen maintenance in AML

Dacogen (decitabine) is a new drug, a DNA methyltransferase inhibitors (DMTI), that approved by the FDA for use in all French- American British (FAB) categories for MDS. This drug is now FDA approved for MDS.

For acute myelogenous leukemia (AML), less is known. A 2007 review, looked at 33 patients with the World Health Organization (WHO) criteria of AML that were treated with decitabine alone (23 patients) or in combination with valproic acid (10 patients) as first-line therapy. There were 20 men (61%) and their median age was 72, range 39 to 85. Median bone marrow blasts at study entry was 26%, and 14 (42%) had >30% blasts. There were three different schedules of decitabine IV, which gave a total of 100–150 mg/m2/course over 3–10 days. Of the 33 patients treated, there were 8 CRs (24%) and 9 marrow CR/PR/Hematologic improvement (27%) for a total response rate of 17 (52%). Overall mortality at 4 weeks and 8 weeks was 3% and 15%, respectively. At a median follow-up of 20 months, median survival of the entire group was 12.6 months (95% CI: 6.5–23.0), and 2-year survival was 25% (95% CI: 13–48), which compares favorably to reported AML survival in this age group in the United States. The study concluded that decitabine is an effective and less toxic treatment in this AML age group and may prolong survival compared with supportive care.

MGI Pharma is currently conducting a phase III pivotal trial to evaluate Dacogen in patients with AML. Additional phase II studies are also underway to evaluate alternative dosing regimens for Dacogen in patients with MDS, AML and chronic myelogenous leukemia. For maintenance there is: Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia, NCT00416598

Thus, it is still experimental.

 

  

  

REFERENCES:

  

 

Silverman L, Demakos E, Peterson B, et L. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J. Clin. Oncol 2002; 10: 2241-2252.

 

Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.

 

Kantarjian H, O'Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.

 

Vidaza Maintenance in AML

The issue is the status of maintenance with any single agent drug. The maintenance concept has not been proven.  As for Dacogen, Vidaza is not sufficiently studied to be routinely adopted. The most recent phase II study concluded: "5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients".

The Scottish Medicines Consortium does not recommend azacitidine (Vidaza®) for use within NHS Scotland for the treatment of adults who are not eligible for haematopoietic stem cell transplantation (SCT) with intermediate-2 and high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia (CMML) or acute myeloid leukaemia (AML).

Michael Grövdal et al, Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy, B ritish Journal of Haematology
Volume 150 Issue 3, Pages 293 - 302, 2010

Reference: No. (589/09)
Source: Scottish Medicines Consortium (SMC)
Date published: 12/04/2010 16:30
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/SMC-does-not-recommend-azacitidine-Vidaza-for-MDS-CMML-or-AML/

Thalidomide for angiodysplasia

Angiodysplasias are the cause of GI bleeding in 3–6% of all patients and a common cause of beeeding in the elderly. Thalidomide uas been reproted in a number of case reports qnd case series to reduce the angiodysplasias and GI bleeding. However no prospective studies have been done. The drug is now in a clinical trial: Thalidomide Reduces Arteriovenous Malformation Related Gastrointestinal Bleeding, NCT00389935
The purpose of this study is to determine whether Thalidomide is effective in the treatment of arteriovenous malformations in the gastrointestinal tract.

Asher Korzets , Uzi Gafter , Avri Chagnac , Boris Zingerman , Valeriya Morduchovitz , and Yaacov Ori  Thalidomide: a treatment option for bleeding GI angiodysplasias in dialysed patients NDT Plus Advance Access published on October 1, 2008, DOI 10.1093/ndtplus/sfn070.
NDT Plus 1: 354-356.

Shurafa M, Kamboj G (2003). "Thalidomide for the treatment of bleeding angiodysplasias". Am. J. Gastroenterol. 98 (1): 221–2.

Lebrin, Franck (2010) Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nature Medicine 16(4)

Kamalaporn, Patarapong (2009) Thalidomide for the treatment of chronic gastrointestinal bleeding from angiodysplasias: a case series : . European Journal of Gastroenterology & Hepatology 21(12)