News

Imatinib (Gleevec) improves the ability to proceed with allogeneic stem cell transplantation and improves 5-year overall survival (OS) when used as induction therapy in patients with Philadelphia chromosome positive (Ph ) acute lymphoblastic leukemia

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States.

Non-small cell lung cancer (NSCLC) is diagnosed at an early stage, when it is amenable to surgical resection in approximately 20% to 25% of cases.

In the first in-human study fo human umbilical tissue-derived cells as cell-based therapy for retinal degenerative diseases, all seven patients tolerated the subretinal injection well and had no postoperative visual loss.

The dream that stem cell therapy may someday be used to protect against or restore glaucoma-related vision loss seems to be moving closer to reality.

Patients with advanced non-small-cell lung cancer achieved a significant increase in survival time when tumor treating fields (TTF) therapy was added to their chemotherapy. In a single-arm, phase II study, physicians delivered TTF therapy, using the NovoTTF-100L from Novocure, to 42 patients with stage IIIb-IV metastatic NSCLC who had failed prior treatments. Patients in the study received TTF therapy for 12 hours a day in combination with pemetrexed (Alimta) every three weeks until disease progression.

Research from Japan documenting remarkable survival rates among patients with inoperable lung cancer may only hint at the potential of proton-beam radiation therapy. The study out of the Proton Medical Research Center in Tennoudai, Japan, documented high survival rates for 55 patients suffering from stage I inoperable non-small-cell lung cancer.

Patients with incurable NSCLC are less likely to progress to second-linetherapy with the right maintenance regimen. But maintenance therapyalso means committing patients to continuous treatment without anybreaks or chances to recover from adverse events.

CAL-101 and GA101 demonstrate active results in indolent B-cell non-Hodgkin’s lymphoma and chronic lymphocytic leukemia while a secondary analysis of a pralatrexate (Folotyn) trial shows a benefit for peripheral T-cell lymphoma patients who fail second-line therapy.

The effectiveness of RT in the palliative setting is sometimes overlooked; however, RT can provide excellent palliation for patients whose disease becomes refractory to other modalities.

Despite the fact that elderly patients comprise over 50% of the non-small cell lung cancer (NSCLC) population, our knowledge regarding the efficacy and safety of chemotherapy in this group is suboptimal. The “elderly” (defined as individuals ≥70 years of age) experience physiologically normal aging of their bone marrow and kidneys, which inherently increases toxicity to therapy. Standard practice has often been to discourage the use of combination chemotherapy in these patients; however, general consensus guidelines emphasize that performance status should primarily guide the choice of treatment. Elderly patients with advanced NSCLC treated with platinum doublet therapy demonstrate similar efficacy (but increased toxicity) to their younger counterparts. Patients with metastatic disease in which a targeted and/or biological agent(s) was added to chemotherapy experienced benefits similar to those treated with standard platinum doublets, but with increased morbidity and mortality. In the future, effective testing of molecular targeted therapies will have to include elderly patients among research cohorts or risk excluding a large population of eligible patients. Overall, elderly patients with advanced NSCLC, while experiencing greater toxicity, demonstrate the same response rates and survival benefits as their younger peers.

The role of radiation therapy (RT) in lung cancer is long established; some of the earliest Radiation Therapy Oncology Group reports dealt with non-small cell lung cancer (NSCLC).[1,2] More recently, the advent of stereotactic body RT (SBRT) techniques has provided significant local control rates after focused treatment of selected small metastases and inoperable early stage lesions.[3,4] Our center has been in the forefront of examining SBRT and its role in central [5] or bilateral [6] lesions, its effect on PET imaging [7] and pulmonary function testing,[8] and subsequent frequency of brachial plexopathy,[9] chest wall toxicity,[10] or pneumonitis.[11] Still, even this highly conformal technique comes with potentially significant dose to adjacent normal tissue. This is in the context of an emerging appreciation for the pulmonary consequences of elevated mean lung dose,[12] or V5 after pneumonectomy.[13] For each lung cancer patient requiring RT, an effective mechanism to deliver dose to the tumor while minimizing dose to uninvolved lung is called for. Enter protons.

Proton radiation for cancer offers the ability to conform the high-dose region of radiation therapy to the tumor while reducing the dose of radiation to adjacent normal tissues. In lung cancer, this equates to greater sparing of uninvolved lung, heart, esophagus, and spinal cord. Sparing these normal tissues permits the delivery of higher-radiation doses to the tumor. Studies that compare the distribution of radiation doses for lung cancer show that proton radiation is superior, even when factors such as respiratory motion are considered. Clinical experience confirms the feasibility of proton radiation for early-stage non-small-cell lung cancers, and clinical trials are being conducted in locally advanced tumors: To date, evidence indicates that proton radiation should be further explored.

Until recently, standard treatment of multiple myeloma (MM) in elderly patients who were not candidates for autologous stem cell transplantation was with the combination of melphalan plus prednisone (MP). Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.

XCell-Center's stem cell treatment helps patient avoid knee replacement.

News items reported in this issue: 1) 186-Gene Signature in Cancer Stem Cells Predicts Recurrence 2) National Prostate Cancer Coalition Commences Clinical Trial Education Program 3) Concomitant High-Dose Radiation Therapy Plus Cetuximab Improves Locoregional Control and Reduces Mortality, with No Increase in Radiation Therapy–Associated Toxicity in Patients with Advanced Squamous-Cell Carcinoma of the Head and Neck 4) STAT3 Pathway Inhibitor (Degrasyn) Drug Class Shows Promise in the Treatment of Malignant Brain Tumors

News items reported in this issue: 1) 186-Gene Signature in Cancer Stem Cells Predicts Recurrence 2) National Prostate Cancer Coalition Commences Clinical Trial Education Program 3) Concomitant High-Dose Radiation Therapy Plus Cetuximab Improves Locoregional Control and Reduces Mortality, with No Increase in Radiation Therapy%u2013Associated Toxicity in Patients with Advanced Squamous-Cell Carcinoma of the Head and Neck, and more

Primary surgery with an abdominoperineal resection (APR) was historically the standard of care for localized anal squamous cell carcinoma. APR achieved 40%-70% survival rates at five years, with local failures from 27%-47%.[1,2] With modern technology and radiation dose escalation, external beam radiation therapy (EBRT) studies have improved complete response rates, decreased morbidity, and improved sphincter preservation rates. Nigro et al added 5-fluorouracil (5FU) and mitomycin C (MMC) to concurrent EBRT [3,4] and impressive complete response rates inspired other groups to investigate the role of chemotherapy as a component of sphincter-preserving therapy. The European Organization for Research and Treatment of Cancer (EORTC) and United Kingdom Coordinating Committee on Cancer Research (UKCCCR) studies reported improved local control and colostomy-free survival when chemotherapy (5FU/MMC) was administered in conjunction with radiation.[5,6] The five-year survival rate for patients receiving standard chemoradiation approaches 70%; however, 20%-40% experience grade 3-4 toxicity, and administration with MMC causes profound hematologic toxicity.

The Clinical Trials reported in this issue include: PHASE I: 1) Cell Genesys and Medarex Remain Positive on Combination Immunotherapy Study 2) Active Biotech Achieves Success with TASQ for Prostate Cancer PHASE II: 1) Myriad Initiates Evaluation of Brain Cancer Drug that Crosses the Blood-Brain Barrier 2) Second Lung Cancer Trial Adds Data to Novel Therapy PHASE III: 1) Nexavar Could Soon Add Primary Liver Cancer to its Label 2) Point Therapeutics Provides Clinical Update for NSCLC Studies

The Clinical Trials reported in this issue include: PHASE I: 1) Cell Genesys and Medarex Remain Positive on Combination Immunotherapy Study 2) Active Biotech Achieves Success with TASQ for Prostate Cancer PHASE II: 1) Myriad Initiates Evaluation of Brain Cancer Drug that Crosses the Blood-Brain Barrier 2) Second Lung Cancer Trial Adds Data to Novel Therapy, and more

Induction chemotherapy has led to improved survival and organ preservation. Combining induction therapy with other treatment modalities is critical for treating this complex disease and attaining optimal outcomes.

Data from French trial should inform treatment decisions in the majority of lung cancer patients aged 70 and up.

A preclinical study provides the rationale for combining BRAF-targeted therapy with immunotherapy agents in patients with BRAF mutations. These mutations activate the MAPK signaling pathway, which leads to increased oncogenic potential. The researchers showed that in BRAF-mutant melanoma cell lines, a selective BRAF inhibitor (PLX4720) blocked the MAPK pathway and increased tumor antigen expression without affecting T-cell function.

Drug is indicated for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy.

Physicians' Financial News focuses on newsmaking and/or notable companies in the oncology/biotech sector. In this issue: 1) Pharmion: Oncology-Centered Focus Fuels Continued Pharmion Growth 2) Bristol-Myers Squibb: Treatment-Resistant Breast Cancer Targeted 3) Merger-Mania Poised to Envelop Biotech Sector? 4) GlaxoSmithKline: Oral Therapy Option Offered for Small-Cell Lung Cancer Relapse 5) Immunomedics,Inc.: Immunomedics Wins Pancreatic Cancer Patent 6) ZymoGenetics: Promising Kidney Cancer Therapy Moves Toward Phase II

Topics covered in this issue include:1) Dosing Patterns and Costs of Erythropoesis-Stimulating Agents in Patients With Cancer2) New Practice Guideline Updates Treatment of Nonâ%uFFFD%uFFFDSmall Cell Lung Cancer3) Large Health Insurer Begins Genetic Risk Counseling for Cancer4) Multiple Myeloma Guidelines Now Include Combination Therapy With Bortezomib5) Survey Finds That Managed Car Executives Are Misinformed About the Value and Cost of Cancer Biologics

The Clinical Trials reported in this issue include: PHASE III: 1) What Factors Predict Prognosis in Patients With Malignant Pleural Mesothelioma? 2) Treatment for Patients With High-Risk Postoperative Breast Cancer PHASE II: 1) Epratuzumab Plus Rituximab Equals Non-Hodgkin's Lymphoma Response 2) Topotecan Added to Twice-Daily Chemoradiation to Treat Limited- Stage, Small-Cell Lung Cancer 3) First-Line Therapy for Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer 4) Radiotherapy for Nasal Squamous Cell Carcinoma Therapy PHASE I/II: 1) A New Combination Approach for Advanced-Stage Germ-Cell Tumors

Articles in this issue include: 1) South Korea: Is Intermittent Imatinib Therapy for Chronic Myelogenous Leukemia an Option? Genetic Marker Predicts Treatment Resistance and Poor Outcomes in Esophageal Cancer 2) France: Pelvic Radiation in Addition to Prostate Radiotherapy for Localized Prostate Cancer 3) Multiple Sites in Europe: European Guidelines for Oral Mucositis Released 4) Japan: The Care of Delirium in Terminal Illness and Bereavement Needs 5) The Netherlands: Cancer Pain and Adherence to Analgesic Treatment 6) Switzerland, Belgium & France: Confirmation of Gene Expression Link to Chemotherapy Response in Breast Cancer

Clinical Trial Reports in this issue include: Phase IV: 1) Long-Term Aspirin Therapy Reduces Colorectal Cancer Risk Phase III: 1) Does Adding Cisplatin to Adjuvant Chemotherapy Improve Outcomes in Advanced Gastric Cancer? 2) FOLFIRI Plus Bevacizumab Provides Better Survival Than Other Irinotecan-Containing Regimen in First-Line Colorectal Cancer Phase II: 1) Single-Agent Activity of Sunitinib in Refractory Non������¢���¯���¿���½���¯���¿���½Small Cell Lung Cancer 2) The Importance of Targeting Androgen Receptor Signaling for Prostate Cancer Response Rate 3) Improving Survival in Gastrointestinal Stromal Tumor 4) Improving Overall Survival in Patients With Hormone- Resistant Prostate Cancer 5) Breast Cancer Stem Cells Decreased With Neoadjuvant Lapatinib Phase I/II: 1) Patients With Recurrent Glioblastoma May Benefit From Implant Combinations