News

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.

;In patients with newly diagnosed multiple myeloma, the addition of bortezomib (Velcade) to thalidomide (Thalomid) and dexamethasone significantly increased response rates, compared with thalidomide plus dexamethasone alone, when used as induction therapy prior to autologous stem cell transplant (ASCT

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

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.

A MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) showed very encouraging activity in the postoperative adjuvant treatment of non-small-cell lung cancer (NSCLC) in a multicenter, double-blind phase II European study

Millennium Pharmaceuticals, Inc. has initiated a randomized, multicenter, company-sponsored phase III trial to determine the most effective Velcade (bortezomib)-based combination therapy with approved agents for the treatment of newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation

Anastrozole (Arimidex): Conversion to regular approval for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. Issued September 2005.Bevacizumab (Avastin): Treatment of metastatic colon cancer. Issued June 2006. Bortezomib (Velcade): Treatment of previously treated mantle cell lymphoma. Issued December 2006. Capecitabine (Xeloda): Single-agent adjuvant treatment of Dukes’ stage C colon cancer in patients who have undergone complete resection of the primary tumor and for whom fluoropyrimidine therapy alone would be preferred. Issued June 2005. Cetuximab (Erbitux): For use in combination with radiation therapy for the treatment of patients with unresectable squamous cell cancer of the head and neck and for patients whose disease has metastasized despite use of standard chemotherapy. Issued March 2006. Dasatinib (Sprycel): Treatment of chronic myelogenous leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia. Issued June 2006. Decitabine (Dacogen): Treatment of myelodysplastic syndromes. Issued May 2006. Docetaxel (Taxotere): In combination with cisplatin and fluorouracil prior to radiotherapy for treatment of inoperable locally advanced squamous cell carcinoma of the head and neck. Issued October 2006. Erlotinib (Tarceva): Treatment of locally advanced or metastatic non–small-cell lung cancer following failure of at least one prior chemotherapy regimen. Issued November 2004; In combination with gemcitabine for first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer. Approved for this indication November 2005. Exemestane (Aromasin): Adjuvant treatment of postmenopausal women with estrogen receptor positive early breast cancer who have received 2 or 3 years of tamoxifen therapy and are switched to exemestane for completion of 5 years of adjuvant hormonal therapy. Issued October 2005.Gefitinib (Iressa): AstraZeneca and FDA approved new labeling for gefitinib limiting its use to cancer patients who are currently benefiting or have previously benefited from treatment with this agent. Distribution limited under a risk-management plan called Iressa Access Program. Issued June 2005.Gemcitabine (Gemzar): In combination with carboplatin for treatment of ovarian cancer. Issued July 2006.Lapatinib (Tykerb): Treatment in combination with capecitabine of advanced or metastatic breast cancer (HER2-positive). Issued March 2007.Lenalidomide (Revlimid): Treatment of patients with deletion 5q cytogenetic abnormality subtype of myelodysplastic syndrome. Issued December 2005. Treatment of multiple myeloma. June 2006.Letrozole (Femara): Adjuvant treatment of postmenopausal women with hormone-receptor-positive early breast cancer. Issued January 2006.Nelarabine (Arranon): Accelerated approval for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Patients must have had failure of at least two prior chemotherapy regimens. Issued October 2005.Panitumumab (Vectibix): Treatment of colorectal cancer that has metastasized following standard chemotherapy. Issued September 2006. Pegaspargase (Oncaspar): Treatment of acute lymphoblastic leukemia in adults and children. Issued July 2006. Rituximab (Rituxan): First-line treatment of diffuse large B-cell, CD20 positive, non-Hodgkin’s lymphoma in combination with CHOP or other anthracycline-based chemotherapy regimens. Issued February 2006. Sorafenib (Nexavar): Treatment of advanced renal cell carcinoma in adults. Issued December 2005.Sunitinib maleate (Sutent): Treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Also accelerated approval for the treatment of advanced renal cell carcinoma based on partial response rates and response duration. Issued January 2006. Approved for first-line treatment of advanced renal cell carcinoma. Issued February 2007.Thalidomide (Thalomid): Treatment of multiple myeloma. Issued May 2006.Topotecan (Hycamtin): Treatment of cervical cancer. Issued June 2006.Trastuzumab (Herceptin): Expanded use of trastuzumab post surgery in combination with other cancer drugs for treatment of HER-2 positive early breast cancer. Issued November 2006.Vorinostat (Zolinza): Treatment of cutaneous manifestations of progressive, recurrent cutaneous T-cell lymphoma. Issued October 2006.

Approximately one-third of patients with non-small cell lung cancer (NSCLC) present with locally advanced disease, the majority of whom are treated with concurrent chemotherapy and thoracic radiation therapy. Concurrent chemoradiation therapy is superior to sequential chemotherapy followed by thoracic radiation therapy or thoracic radiation therapy alone.

Paralleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell cancer (RCC).

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.