News

BOSTON-A gene therapy agent that delivers a normal p53 gene to the tumor significantly increased survival by 4.5 months in end-stage head and neck cancer patients with p53-favorable tumor profiles, compared to those with unfavorable profiles.

A large phase III study has found that the targeted therapy cetuximab (Erbitux), combined with platinum-based chemotherapy, is effective as a first-line treatment for patients with advanced non–small-cell lung cancer (NSCLC). This is the first time a targeted drug has shown a survival benefit as a first-line treatment for patients with NSCLC, including all subtypes of the disease, reported lead author Robert Pirker, md, associate professor of medicine at Medical University of Vienna in Austria at the ASCO meeting (abstract 3).

One of the first clinical trial's of a revolutionary gene therapy for Leber's congenital amaurosis (LCA), a type of inherited blindness, showed that the treatment can improve vision and cause no side effects.

The appropriate treatment of patients with stage IIIA (N2) non–small-cell lung cancer (NSCLC) is unclear. With this case report and review, we address the history, assessment, and management of a 67-year-old patient with this diagnosis, and then discuss the challenges in managing N2 disease, as well as the roles of systemic therapy, surgery, and postoperative radiation therapy.

In results that challenge conventional models for color vision circuitry, researchers used gene therapy in a dichromatic primate model to add a third photopigment and bring about red-green vision. This successful treatment of adult monkeys with a congenital color vision defect shows that the adult nervous system can respond to newly added sensory input and is encouraging for the possibility of using gene therapy to treat various cone-based vision disorders in human adults, said Katherine Mancuso, MD, of the Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.

Drs. Rini and Bukowski do an excellent job of updating and commenting on the rapidly evolving field of therapy for metastatic renal cell carcinoma (RCC).

Recent advances in the understanding of the biology of renal cell carcinoma (RCC) have been translated into clinical treatment options in metastatic disease.

Cisplatin is effective in treating several types of childhood cancers (eg, CNS tumors, osteosarcoma, hepatoblastoma, neuroblastoma, germ cell tumors). It is the most ototoxic drug used clinically, and hearing loss is a well-recognized toxicity of cisplatin therapy.

Drs. Kelsey, Marks, and Wilson open their excellent review article by asking “Where do we stand?” with respect to postoperative radiation therapy (PORT) for non–small-cell lung cancer (NSCLC).[1] Frankly, PORT has not exactly been standing tall for the past decade-leaning, crouching, or perhaps squatting might be a better verb.

Positron emission tomography (PET) can be used to better characterize patterns of local failure after definitive radiation therapy for non-small-cell lung cancer, which may help to improve that therapy

Patients with early-stage diffuse large B-cell lymphoma (DLBCL) have improved long-term disease-free and overall survival if their first-line treatment includes radiation therapy, according to the largest outcomes study to date among this population.

A 68-year-old man with a history of small-cell lung cancer with bony metastases was admitted with diarrhea. The patient had completed chemotherapy one week earlier with cisplatin and etoposide, along with radiation therapy, and irinotecan (Camptosar). The patient was found to be neutropenic.

When used as adjuvant therapy for node-positive breast cancer, the combination of high-dose chemotherapy (HDC) and stem cell transplantation modestly improves relapse-free survival relative to standard-dose chemotherapy (SDC). But it offers at best minimal benefit in terms of overall survival, according to a meta-analysis presented at SABCS.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

A significant proportion of patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. For the most part, fit patients with this diagnosis are treated with combined-modality therapy. Relatively few are rendered resectable. Over the past two decades, combination chemotherapy and radiation, preferably concurrent chemoradiation, has emerged as the standard of care. However, survival gains have been offset, to some extent, by local, normal-tissue, in-field toxicity, particularly esophagitis and pneumonitis.

Hematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.

Hematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.

Hematopoietic stem cell (HSC) transplantation may improve outcomes of patients with hematologic malignancies not curable with conventional therapies. In some clinical settings, transplantation represents the only curative option. The feasibility and efficacy of this approach in older patients are undefined, since this population has been excluded from nearly all clinical trials. Advances in supportive care, HSC harvesting, and safer conditioning regimens have made this therapy available to patients well into their 6th and 7th decades of life. Recent evidence suggests that elderly patients with good performance status and no comorbidities could, in fact, not only survive the transplant with reasonable risk, but also benefit in the same measure as younger patients.

Although significant advances have been made in the systemic therapy of non–small-cell lung cancer (NSCLC) in patients with a good performance status (PS), the subgroup of patients with a poor PS has not been studied as well.

Rituximab (Rituxan) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard induction therapy for patients with advanced-stage diffuse large B-cell lymphoma, including both elderly and younger patients.

Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.Genzyme Corp and Bayer HealthCare Pharmaceuticals Inc announced that the US Food and Drug Administration (FDA) has approved a supplemental biologics license application (sBLA) for alemtuzumab (Campath) and granted regular approval for single-agent alemtuzumab for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.

An experimental gene therapy targeting pancreatic cancer reduced or eradicated tumors, inhibited metastasis, and prolonged survival in experiments in two mouse models, and did so with very limited toxicity.

It may soon be possible to determine which breast cancer patients will respond to adjuvant endocrine therapy, based on the level of cell-cycle response in the surgical specimen after neoadjuvant endocrine therapy

High-dose combination chemotherapy followed by autologous peripheral-blood stem cell transplant produced durable remissions in metastatic testicular cancer patients who relapsed or failed to respond to traditional therapy