OFFICIAL TRIAL NAME

"An Open-Label, Randomized, Phase 3 Trial of Intravenous Temsirolimus (CCI-779) at Two Dose Levels Compared to Investigator's Choice Therapy in Relapsed, Refractory Subjects With Mantle Cell Lymphoma (MCL)."

PUBLICATION

The Journal of Clinical Oncology, official journal of the American Society of Clinical Oncology.

LEAD STUDY AUTHOR

Georg Hess, MD, Department of Hematology/Oncology, Johannes Gutenberg-University, Langenbeckstr 1, Mainz, DE 55101.

PATIENTS

Aged 18 and older with relapsed or refractory mantle cell lymphoma (MCL).

DRUG AND REGIMEN

Drug: Temsirolimus. Currently it is only FDA-approved for the treatment of renal cell carcinoma, a type of kidney cancer.
Target regimen: Temsirolimus 175 mg weekly for three weeks followed by 75 mg weekly. This is substantially higher than the recommended dosage (25 mg weekly) of temsirolimus.

RESULTS

Median PFS (progression free survival) in:
The temsirolimus 175 mg/75 mg group: 4.8 months
The investigator’s choice group: 1.9 months

Median OS (overall survival) rate with:
Temsirolimus 175 mg/75 mg group: 12.8 months
Investigator’s choice group: 9.7 months

Objective response rate
In the temsirolimus 175 mg/75 mg group: 22%
In the investigator’s choice therapy group: 2%

ADVERSE EVENTS (SIDE EFFECTS)

Eighty-nine percent of the patients receiving the target regimen of temsirolimus 175 mg/75 mg experienced grade-3 or grade-4 adverse events including thrombocytopenia, anemia, neutropenia and asthenia.

CONCLUSION

"Temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly significantly improved PFS and objective response rate compared with investigator's choice therapy in patients with relapsed or refractory MCL."

Source: Hess G. J Clin Oncol. 2009;27:3822-3829

The U.S. Food and Drug Administration has approved GlaxoSmithKline's monoclonal antibody ofatumumab (to be marketed as Arzerra) for the treatment of chronic lymphocytic leukemia (CLL) in patients whose cancer is considered relapsed or refractory.

The FDA approved ofatumumab under its accelerated approval process.

“The approval of Arzerra illustrates FDA's commitment to using the accelerated approval process to approve drugs for patients who have limited therapeutic options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research.

Side effects or adverse events associated with ofatumumab include increased risk of developing progressive multifocal leukoencephalopathy (PML), a brain infection that is generally fatal. This makes Arzerra at least the second monoclonal antibody with potential links to PML, the other being the widely used Rituxan (rituximab).

Those patients considered at high risk for Hepatitis B should be screened before being treated with ofatumumab. Patients with evidence of inactive hepatitis should be monitored for re-activation of the infection during and after completing treatment.

The question is whether this extends to small lymphocytic lymphoma (SLL), as even the World Health Organization considers CLL and SLL to be the same disease.

Ofatumumab is in trials to test its efficacy in treating both follicular lymphoma and diffuse large b-cell lymphoma.

Source: FDA press release

Being prepared for office visits assists your doctor in determining your medical needs and most appropriate treatment plan; helps you receive timely access to medical care and related services, and created a mutually respectful and supportive relationship. Besides bringing along a companion, one if the best ways to prepare for a visit is prepare a concise list of written questions. Provide a copy for your doctor.

• o What is my diagnosis? And can you please provide me a copy of the pathology report.
• o How widespread is the disease (the stage)?
• o Does the disease require prompt treatment and why?
• o Can the disease be cured?
• o What are the symptoms of the disease, and which indicate a need for treatment?
• o What are my treatment choices?
• o Do you offer radioimmunotherapy as a treatment option?
• o Are new treatments under study? Would a clinical trial be appropriate for me?
• o Which treatment or treatment sequence do you recommend? Why? NOTE: The rationale for a treatment can be especially important to you when there are multiple choices and there is no clear best approach.
• o What is your level of confidence that the recommended treatment is the best choice?
• o What is the goal of this treatment? (management versus durable remission)
• o What are the chances that the treatment will be successful?
• o Is the collection of stem cells indicated before or after this treatment? When is the best time to consider stem cell harvesting, in general?
• o How long will the treatments last?
• o How long will it take for the treatment to begin working against the disease? EXAMPLES: Antibiotic therapy for H-pylori can take 12 months or more to show a result against MALT lymphoma; and Rituxan therapy can take many months before an optimal response is seen.
• o How easy is it to administer; will it disrupt my normal life or ability to work?
• o How durable is the response likely to be?
• o What signs will indicate that the therapy is beginning to work or that it is not working?
• o What tests will be used to measure or gauge an early response to treatment?

Dr. Richard Van der Jagt of Ottawa General Hospital presented results from phase II and phase III clinical studies of pixantrone at this weekend's Lymphoma and Myeloma 2009 Conference (October 22-24 2009).

PIXANTRONE

Drug class: Anthracenediones. The only other drug in this class is mitoxantrone. In fact, pixantrone is a less-toxic analogue of mitoxantrone.
Classification: Type II topoisomerase inhibitor. This means it interferes with enzymes that control DNA structure, causing breaks in the DNA and leading to cell death. Etopiside and doxorubicin are topoisomerase II inhibitors.
Current status: FDA fast track; could be available in 2010

PERFORMANCE IN CLINICAL TRIALS

Phase II and phase III clinical studies showed that pixantrone performed pretty well when used in combination with other drugs:

Patients with: Relapsed/refractory indolent NHL
Combination: FPD-R regimen (fludarabine, pixantrone, dexamethasone, rituximab)
Complete remission: 70%

Patients with: Relapsed/refractory aggressive NHL where CHOP failed
Combination: CPOP regimen (cyclophosphamide, pixantrone, vincristine, prednisone)
Complete remission: 47%

Patients with: Relapsed/refractory indolent NHL
Combination: Pixantrone + rituximab
Complete remission: 35%

COMMENTARY

"The results from the pixantrone clinical trials are impressive and indicate the potential for this drug to meet a significant unmet medical need in patients with relapsed or refractory NHL," said Dr. Gary Schiller of the UCLA School of Medicine. "These patients have few options and the availability of an effective treatment would be well received."

Source: Medical News Today by way of Cell Therapeutics, Inc

Marie L. De Bruin, Ph.D., of the Netherlands Cancer Institute in Amsterdam, and colleagues studied 1,122 females who had been treated for Hodgkin's lymphoma with radiation prior to the age of 51 years. The incidence of breast cancer in the cohort was compared to the general population.

Overall, the researchers found that the incidence of breast cancer in the study cohort 30 years after Hodgkin's lymphoma radiation treatment was 19 percent, while for those treated before age 21 years, the incidence was 26 percent. Risk of breast cancer varied by radiation treatment type, with mantle field irradiation of the axillary, mediastinal, and neck nodes producing a 2.7-fold increased risk compared with mediastinal irradiation at similar doses. Women with 20 or more years of ovarian function after radiation therapy at age less than 31 years had higher risk of breast cancer than those with fewer than 10 years of ovarian function.