Oncology NEWS International Vol 12 No 2

COX-2 Inhibitors Decrease Toxicity due to Chemotherapy; May Help Arrest Tumor Progression

February 01, 2003

HOUSTON-Inflammation is a common link between the toxicity of chemotherapy and cancer progression, and the possibility that anti-inflammatory treatments might help both is attracting more research attention. "Cancer is a nonhealing wound with persistent inflammation," Edward H. Lin, MD, said, quoting Harold Dvorak, MD, of Beth Israel Hospital in Boston. Dr. Lin is assistant professor of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Some Activity for Gefitinib in Heavily Pretreated Breast Cancer

February 01, 2003

SAN ANTONIO-In the first phase II trial of gefitinib (Iressa, also known as ZD1839) in breast cancer, the agent showed limited activity in patients with heavily pretreated metastatic breast cancer, according to a report presented at the 25th Annual San Antonio Breast Cancer Symposium (abstract 20).

Brachytherapy Results Similar for Blacks, Whites

February 01, 2003

CHICAGO-Black men with localized prostate cancer do just as well as white men when treated with brachy-therapy alone, William Barrett, MD, said at the 88th Annual Scientific Assembly of the Radiological Society of North America (RSNA abstract 252RO-p).

Dose-Dense Chemo Ups Survival in Node+ Breast Cancer

February 01, 2003

SAN ANTONIO-A condensed, 14-day schedule of doxorubicin (Adria-mycin), cyclophosphamide, and pacli-taxel (Taxol) proved superior to conventional scheduling of the three drugs in a Cancer and Leukemia Group B (CALGB) trial reported at the 25th Annual San Antonio Breast Cancer Symposium (abstract 15). According to study investigator Marc L. Citron, MD, the dose-dense scheduling resulted in significant improvements in both disease-free and overall survival-and, with filgrastim (Neupogen) support, did not increase drug toxicity.

MR Spectroscopy IDs Breast Cancers, Node Involvement

February 01, 2003

ORLANDO-A computer-based diagnostic system for breast cancer using magnetic resonance spectroscopy (MRS) plus a statistical classification strategy (SCS) is ready for acceptance testing in the clinic, Australian researchers said at the Era of Hope Department of Defense Breast Cancer Research meeting.

ODAC Wants More Data on Expanded Casodex Indication

February 01, 2003

BETHESDA, Maryland-Astra-Zeneca failed to gain backing from the FDA’s Oncologic Drugs Advisory Committee (ODAC) for its effort to expand the indication for Casodex (150 mg bicalutamide) in the treatment of prostate cancer. ODAC members found that the data presented were too premature to recommend that the FDA approve the company’s supplementary new drug application. They suggested, instead, that the agency delay a decision until longer-term data about the drug’s efficacy become available.

SuperGen Submits First NDA Module for Pancreatic Cancer Drug

February 01, 2003

DUBLIN, California-Super-Gen Inc. has begun submission of a New Drug Application (NDA) for Orathecin, an oral camptothecin, for the treatment of pancreatic cancer patients who are refractory/resistant to available therapies. The submission will occur on a rolling basis and is ex-pected to be completed by the end of the first quarter of 2003. The submission will contain data on more than 2,700 patients treated under Orathecin study protocols, the company said in a news release.

Two Added to ONI’s Oncology Nursing Editorial Advisory Board

February 01, 2003

MELVILLE, New York-ONI is pleased to announce the addition of two new members to its recently created Editorial Advisory Board for Oncology Nursing: Genevieve V. Foley, RN, MSN, OCN, CNAA, and Mary Pazdur, RN, MSN, ANP, AOCN. The two will work with Sharon Krumm, PhD, RN, Editor of Oncology Nursing, and current nursing board members Catherine Coleman, RN, OCN, and Mary McCabe, BSN, MA (see ONI January 2003, page 27).

Bortezomib Active in Relapsed/Refractory Myeloma

February 01, 2003

PHILADELPHIA-Two phase II clinical trials presented at the 44th Annual Meeting of the American Society of Hematology (ASH) have established the activity of the investigational proteasome inhibitor bortezomib (Velcade, also known as PS-341, Millennium Pharmaceuticals) in relapsed or refractory multiple myeloma.

Telomerase Potential Cancer Biomarker

February 01, 2003

SEATTLE-Telomerase may be an early biomarker of pancreatobiliary malignancies, and telomerase enzyme immunostaining represents a potential breakthrough in screening for and diagnosing cancer in patients with biliary strictures, Tarun Mullick, MD, said at the president’s plenary session of the 67th Annual Meeting of the American College of Gastroenterology (ACG abstract 3).

Developing Targeted Therapy More Difficult Than Anticipated

February 01, 2003

BETHESDA, Maryland-Cell signaling pathways offer many potential targets for antitumor therapies, but hitting those targets is proving more difficult than researchers had anticipated, according to John J. Wright, MD, PhD. He is senior clinical investigator, Investigational Drug Branch, Cancer Therapy Evaluation Program, at the National Cancer Institute in Bethesda, Maryland.

Preoperative Chemoradiotherapy Downsizes 100% of Rectal Tumors in Phase I/II Trial

February 01, 2003

PHILADELPHIA-Preoperative chemoradiotherapy with irinotecan (CPT-11, Camptosar), fluorouracil (5-FU), and radiation showed a significant ability to downsize rectal adenocarcinomas and is being studied further in clinical trials, Edith P. Mitchell, MD, reported. Due to problems associated with the central venous access required for continuous infusion 5-FU, capecitabine (Xeloda) is being substituted for 5-FU in ongoing studies. Dr. Mitchell is clinical professor of medicine at Thomas Jefferson University in Philadelphia.

Fluorouracil/Leucovorin Maintains Leading Role, Results of Three-Drug Regimens Are Pending

February 01, 2003

ROCHESTER, Minnesota-Summarizing cooperative group approaches to adjuvant treatment of colorectal cancer, Charles Erlichman, MD, noted: "Treatment for stage II colon cancer remains controversial. Treatment for stage III colon cancer should be fluorouracil (5-FU)/leucovorin. Treatment for stage III rectal cancer should be radiation plus fluorouracil/leucovorin. The results of three-drug regimens are pending, as are data on the role of COX-2 inhibitors and of targeted agents such as epidermal growth factor receptor (EGFR) or tyrosine kinase inhibitors." Dr. Erlichman is professor of oncology, Mayo Clinic, Rochester, Minnesota.

Adjuvant Therapy for Rectal Cancer Still Needed in Node-Positive Cases

February 01, 2003

NEW YORK-Total mesorectal excision (TME) has reduced the risk of local recurrence in rectal cancer, but adjuvant therapy is still needed in node-positive cases, according to Bruce Minsky, MD, vice chairman of radiation oncology at Memorial Sloan-Kettering Cancer Center in New York.

Adding Bevacizumab to IFL Combination Does Not Significantly Alter IFL Toxicity

February 01, 2003

PHILADELPHIA-Bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor (VEGF), was well tolerated in preliminary analyses of two Eastern Cooperative Oncology Group (ECOG) studies, according to Bruce J. Giantonio, MD, assistant professor of medicine, University of Pennsylvania Medical Center, Philadelphia.

European Studies Compare Combination Regimens Against Advanced Colorectal Cancer

February 01, 2003

NANTES, France-European researchers are moving beyond colorectal cancer regimens based on infusional fluorouracil (5-FU) to comparing combinations and to examining the effects of scheduling on response and time to progression, according to Jean-Yves Douillard, MD, PhD. Professor Douillard, who developed a widely-used regimen for colorectal cancer, is professor of medical oncology and head of the department of medical oncology, Centre Rene Gauducheau, at the University of Nantes in France.

Task Force Does Not Recommend Routine Prostate Cancer Screening

February 01, 2003

ROCKVILLE, Maryland-The US Preventive Services Task Force has concluded that not enough scientific evidence exists to promote routine screening of all men over age 40 for prostate cancer via standard PSA test and/or digital rectal exam. The task force-sponsored by the Agency for Healthcare Research and Quality-concluded that the tests are effective for diagnosis but that there is insufficient evidence to show that they affect long-term health or survival. The task force noted that results of the ongoing Prostate, Colorectal, Lung, and Ovarian Screening Trial, designed to answer this question, will not become available until later in this decade.

IFL Regimen Dosages and Schedules Adjusted to Decrease Toxicity

February 01, 2003

NEW YORK-By tinkering with both dosage and scheduling, researchers are hoping to shift the balance of benefits over toxicity in patients treated with irinotecan/fluorouracil/leucovorin (IFL). Variations being tried include moving to a day 1, day 8 schedule every 21 days with day 15 as a rest day, and reducing starting doses for particular patient groups, David H. Ilson, MD, PhD, reported. Dr. Ilson is associate attending physician at Memorial Sloan-Kettering Cancer Center and assistant professor of medicine at Weill Medical College of Cornell University in New York.

Upfront Neoadjuvant Therapy Urged for All Colorectal Cancer Patients With Liver Metastases

February 01, 2003

BALTIMORE-Between 11,000 and 12,000 colorectal cancer patients present with liver metastases each year. Surgical resection is ideal but does not remove microscopic metastases and disease left behind after surgery. "Today, treatment should start with neoadjuvant therapy in all colorectal cancer patients that have liver metastases," Yehuda Z. Patt, MD, said.

Treating Mild Anemia Reduces Fatigue, Clinic Visits

February 01, 2003

PHILADELPHIA-Chemotherapy patients whose hemoglobin (Hb) drops below 9 g/dL are typically treated with recombinant human erythropoietin, but those whose anemia is in the 10 to 12 g/dL range are typically not given hematopoietic support.

Sequential Fludarabine/Alemtuzumab in High-Risk CLL

February 01, 2003

PHILADELPHIA-Early results of a phase II trial of sequential fludarabine (Fludara)/alemtuzumab (Campath) therapy in patients with high-risk chronic lymphocytic leukemia (CLL) are encouraging in that the monoclonal antibody appears to improve the rate of flu-darabine-induced responses, Dr. Kanti R. Rai said at the 44th Annual Meeting of the American Society of Hematology (abstract 772). This study is one of several Cancer and Leukemia Group B (CALGB) trials investigating the combination of fludarabine, an effective single-agent therapy for CLL, with various antineoplastic monoclonal antibody agents.

Trials Suggest Capecitabine Might Be Simpler Substitute for 5-FU in Colorectal Cancer Regimens

February 01, 2003

GLASGOW, Scotland-"Development of capecitabine (Xeloda) was inspired by the fact that what is wanted is an oral tablet that will mimic infusional fluorouracil (5-FU) and will have tumor-selective activation. Clearly, about 90% of patients prefer oral therapy, but they do not want to sacrifice efficacy for convenience," Christopher Twelves, MD, stated. A number of recent clinical trials suggest that capecitabine might be a simpler substitute for 5-FU in colorectal cancer regimens and Dr. Twelves, a consultant in medical oncology at Cancer Research UK, Glasgow, Scotland, discussed this possibility at the First International Colorectal Cancer Congress in Palm Beach, Florida.

ILEX Begins Phase I/II Trial of Campath in CD52-Positive NHL

February 01, 2003

SAN ANTONIO-ILEX Oncology, Inc. has launched the first ILEX-sponsored study of Campath (alemtuzumab) in patients with CD52-antigen-positive relapsing or refractory non-Hodgkin’s lymphoma (NHL). Campath is a humanized monoclonal antibody directed against the CD52 antige

Ethnic Differences in Breast Cancer Treatments, Outcomes

February 01, 2003

SEATTLE-A Fred Hutchinson Cancer Research Center study documents important disparities in breast cancer diagnosis, treatment, and survival among American women of various ethnicities. The findings by Christopher Li, MD, PhD, and his colleagues (Arch Intern Med 163:49-56, 2003) are based on data from 11 tumor registries participating in the Surveillance, Epidemiology, and End Results (SEER) program, including 124,934 women diagnosed with first primary invasive breast cancer from 1992 to 1998.

Simultaneous Fludarabine/Alemtuzumab in Relapsed CLL

February 01, 2003

PHILADELPHIA-A four-cycle regimen of simultaneous combined flu-darabine (Fludara) and alemtuzumab (Campath) (FLUCAM) was effective in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL), according to a poster presentation at the 44th Annual Meeting of the American Society of Hematology (abstract 3169). [See page 42 for another ASH presentation on these two agents in CLL.]

Guidelines May Improve Clinical Outcome for Chemotherapy-Induced Diarrhea

February 01, 2003

NEW YORK-"Chemotherapy-induced diarrhea remains a serious clinical problem, but newer guidelines may improve the clinical outcome for this syndrome," Scott Wadler, MD, said. He is head of the solid tumor service at Cornell University’s Weill Medical College in New York.

Chemoradiotherapy Trial With Capecitabine and Recombinant Erythropoietin to Start Soon

February 01, 2003

PITTSBURGH-Attempts to conduct randomized comparative trials of preoperative vs postoperative therapy for rectal cancer have been largely unsuccessful in the United States. Many surgeons have already decided which approach they are committed to and will not randomize patients to the alternate approach, according to Roy E. Smith, MD. As director of medical affairs and oversight for the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation in Pittsburgh, Dr. Smith has had experience in NSABP’s efforts to get comparative trials off the ground.

Sharp Mesorectal Excision Is Now Recommended for All Rectal Cancers

February 01, 2003

LEXINGTON, Kentucky-Inadequate surgical resection is emerging as a major cause of recurrence in rectal cancer, and most such recurrences could be prevented by use of sharp mesorectal excision (SME) rather than blunt dissection, according to Alfred M. Cohen, MD. Dr. Cohen, director of the Lucille P. Markey Cancer Center at the University of Kentucky in Lexington, reviewed state-of-the-art rectal cancer surgery.

ODAC Cites Clinical Benefits of Bexxar, Safety Concerns

February 01, 2003

BETHESDA, Maryland-Members of the FDA’s Oncologic Drugs Advisory Committee (ODAC) gave a mixed review to Corixa’s Bexxar (tositumomab and iodine I-131-tositumomab), a radioactive-labeled monoclonal antibody intended to treat certain non-Hodgkin’s lymphoma (NHL) patients.

Bcl-2 Antisense Response in Melanoma Called ‘Remarkable’

February 01, 2003

NEW YORK-An antisense oligonucleotide directed against Bcl-2 is yielding "remarkable" responses in specific melanoma patients enrolled in a phase III trial, according to Anna C. Pavlick, DO, assistant professor of medicine, New York University School of Medicine.

Phase I/II Trials Suggest Capecitabine Could Be Good Partner When Used With Oxaliplatin or Irinotecan

February 01, 2003

NEW HAVEN, Connecticut-Capecitabine (Xeloda) was developed as an oral tumor-activated alternative to fluorouracil (5-FU) and now appears set to replace that agent in some combination regimens for colorectal cancer according to Edward Chu, MD. Dr. Chu reported that phase II trials suggest that either capecitabine/oxaliplatin (Eloxatin) or capecitabine/irinotecan (CPT-11, Camptosar) might be effective replacements for 5-FU-based regimens. Dr. Chu is professor of medicine and pharmacology at Yale University School of Medicine and associate director of the Yale Cancer Center, New Haven, Connecticut.

Novel Glutathione Leads to Longer Ovarian Cancer Survival

February 01, 2003

NEW YORK-Previously treated patients with ovarian cancer who received a novel glutathione (TLK286, Telik, Inc., San Francisco) have thus far survived a median of more than 56 weeks, according to preliminary results from an ongoing multicenter phase II trial. John J. Kavanagh, MD, presented the results at the Mount Sinai School of Medicine Chemotherapy Foundation Symposium XX.

Docetaxel/Calcitriol in Androgen-Independent Prostate Cancer

February 01, 2003

NEW YORK-In patients with androgen-independent prostate cancer, a pulsed regimen of docetaxel (Taxotere) plus high-dose calcitriol is well tolerated and results in disease response by a variety of standard measures, according to results of a phase II trial.

Metastatic Thyroid Cancer Responds to Thalidomide Therapy

February 01, 2003

NEW YORK-An ongoing trial of thalidomide (Thalomid) in patients with aggressive, advanced papillary and follicular thyroid carcinomas produced an early response rate of 76%, according to a report presented at the Mount Sinai School of Medicine Chemotherapy Foundation Symposium XX.

First-Line Rituximab Produces 72% Response Rate in Follicular NHL

February 01, 2003

PHILADELPHIA-A single four-dose cycle of rituximab (Rituxan) produced an overall response rate of 72% and median progression-free survival of 2.78 years in a phase II trial in patients with newly diagnosed, asymptomatic, advanced-stage follicular grade 1 non-Hodgkin’s lymphoma (NHL).

Carboplatin/TP More Effective Than TP in HER-2+ Breast Cancer

February 01, 2003

SAN ANTONIO-The three-drug combination of carboplatin (Paraplatin), paclitaxel (Taxol), and trastuzumab (Herceptin) increases response rate and time to progression among HER-2-positive patients with advanced breast cancer, compared with the trastuzumab/paclitaxel combination alone, according to Nicholas J. Robert, MD, chairman of research at Inova Fairfax Hospital’s Cancer Center, Fairfax, Virginia, and co-chairman of the Breast Committee of the US Oncology Research Network.

Congress May Revisit Cancer Bills It Failed to Pass in 2002

February 01, 2003

WASHINGTON-The 107th Congress, by general agreement, will not enter the history books as a major contributor to medical and health policy. However, legislation it failed to pass serves as a prologue to some of the issues the new 108th Congress will consider during the next 2 years, said Susan Erickson, acting director of the National Cancer Institute’s (NCI) Office of Policy Analysis and Response. "We will probably continue to see these themes, no matter what specific pieces of legislation come back," she said at a meeting of the National Cancer Advisory Board.

Preoperative Chemoradiation and Aggressive Surgery Effective in Locally Advanced Rectal Cancer

February 01, 2003

HOUSTON-Preoperative chemoradiation and aggressive surgery produced good local disease control and sphincter preservation in patients with locally advanced rectal cancer treated at the University of Texas M.D. Anderson Cancer Center, Houston, but more effective systemic therapy is needed, according to Christopher H. Crane, MD. Dr. Crane, who is assistant professor of radiation oncology at M.D. Anderson, reviewed data from 392 patients with stage II or stage III rectal cancer treated there over the past decade.

Two Experts Describe How They Assess/Manage Fatigue

February 01, 2003

BOSTON-Oncologists should screen cancer patients and survivors routinely for fatigue and attempt to treat those who complain of exhaustion that rest does not relieve, according to two speakers at the 14th international meeting of the Multinational Association for Supportive Care in Cancer (MASCC) and International Association for Oral Oncology.

Advexin p53 Therapy Plus RT Shows Lung Tumor Regression

February 01, 2003

HOUSTON-Introgen Therapeutics, Inc. has published data from its phase II study combining Advexin, an adenoviral vector containing the p53 tumor-suppressor gene, with radiation therapy in patients with nonmetastatic non-small-cell lung cancer (NSCLC) (Clinical Cancer Research, January 2003). The patients were ineligible to receive surgery or combination therapy with radiation and chemotherapy.

Trials Compare Infusional vs Bolus 5-FU/Leucovorin for Adjuvant Treatment

February 01, 2003

NANTES, France-Most ongoing European trials in colorectal cancer are either comparing bolus fluorouracil (5-FU)/leucovorin to infusional 5-FU/leucovorin regimens or comparing infusional 5-FU/leucovorin to combinations with either irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin), according to Jean-Yves Douillard, MD, PhD. He is professor of medical oncology and head of the department of medical oncology at Centre Rene Gauducheau, University of Nantes, France.

Experts Debate Bolus vs Continuous Infusion 5-FU

February 01, 2003

PALM BEACH, Florida-What is the best method for administering fluorouracil (5-FU)? Should it be given as a continuous intravenous infusion, as often done in Europe? Or should 5-FU be administered as an intravenous bolus, as typically done by American physicians, at least partly to avoid the need for central venous access and pump devices.

Oxaliplatin-Based Regimens Prove Active in Advanced Colorectal Cancer

February 01, 2003

NASHVILLE, Tennessee-Regimens that contain oxaliplatin (Eloxatin) as well as irintoecan (CPT-11, Camptosar) and fluorouracil (5-FU)/ leucovorin have produced prolonged survival of 18 to 21 months in patients with advanced colorectal cancer and should be considered for first-line therapy, according to Mace L. Rothenberg, MD. Dr. Rothenberg, who is professor of medicine at Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, reviewed the current status of oxaliplatin-based regimens.

New Agent Blocks Bone Resorption

February 01, 2003

NEW YORK-In phase I trials, AMGN-0007, a new compound to prevent bone metastasis, decreased bone resorption markers to the same extent as the bisphosphonate pamidronate (Aredia), Allan Lipton, MD, professor of medicine, Milton S. Hershey Medical Center, Pennsylvania State University, reported at the Chemotherapy Foundation Symposium XX.

QOL in CML Better With Imatinib Than With Interferon

February 01, 2003

PHILADELPHIA-Chronic myeloid leukemia (CML) patients treated with imatinib mesylate (Gleevec) reported better quality of life (QOL) than those on interferon/cytarabine, and those who switched from interferon/cytarabine to imatinib reported improved QOL, compared with those who remained on interferon, Elizabeth A. Hahn reported. This is clinically important because about 20% of CML patients drop out of interferon treatment within 6 months due to intolerable adverse effects.

When New Drugs Fail: An Analysis of the SU5416 Trial Experience

February 01, 2003

SANTA MONICA, California-Vascular endothelial growth factor (VEGF) offers a number of sites for therapeutic targeting and is thought to play an important role in human cancers. Several angiogenesis inhibitors that work through effects on VEGF are under development, but one that failed in a phase III study may offer important insights for investigators developing this new area of anticancer therapy according to Lee S. Rosen, MD. Dr. Rosen, who was involved in research on the tyrosine kinase inhibitor SU5416, is director of developmental therapeutics, Cancer Institute Medical Group, Santa Monica, California.

Front-Line Regimens That Integrate Irinotecan and Oxaliplatin Produce Median Survival Approaching 3 Years

February 01, 2003

PORTLAND, Oregon-Median survival for patients with advanced colorectal cancer treated with front-line regimens that include irinotecan (CPT-11,Camptosar) or oxaliplatin (Eloxatin) is approaching 3 years. "That is an absolutely remarkable figure to me," said Charles D. Blanke, MD, in a review of new approaches to colorectal cancer treatment. Dr. Blanke is director of the gastrointestinal malignancies program at the Oregon Health Sciences University Cancer Institute in Portland.

Long-Term Survival With Mylotarg/Transplant in AML

February 01, 2003

PHILADELPHIA-Remissions induced by gemtuzumab ozogamicin (Mylotarg) monotherapy in patients with first-relapse acute myeloid leukemia (AML) can be prolonged with subsequent therapy. Allogeneic hematopoietic stem cell transplant was particularly effective and even produced some long-term remissions in patients who did not respond to gemtuzumab, Eric Sievers, MD, reported at the 44th Annual Meeting of the American Society of Hematology (ASH abstract 327).

FDA Approves Gleevec as First-Line Treatment of Patients With CML

February 01, 2003

ROCKVILLE, Maryland-The US Food and Drug Administration (FDA) has approved Gleevec (imatinib mesylate, Novartis) for the first-line treatment of patients with chronic myeloid leukemia (CML) (see January 2003 ONI, page 1). The agency initially approved the drug in May 2001 for treating the advanced stages of CML. Gleevec first received accelerated approval, which required the company to conduct phase IV postmar-keting research to show that the drug provided clinical benefit in advanced CML and to assess its effect in patients with early-stage disease. With its latest action, FDA has now approved Gleevec as therapy for all three stages of CML-blast crisis, accelerated, and chronic-either before or after other therapies.

Erlotinib Is ‘Active, Well Tolerated’ in Pretreated NSCLC

February 01, 2003

NEW YORK-The investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (Tarceva, also known as OSI-774) produced objective remissions and mild toxicity in stage IV non-small-cell lung cancer (NSCLC) patients who had undergone a number of prior chemotherapy regimens, according to results of a phase II study.