Lung Cancer

Fenretinide (N-4-hydroxyphenyl-retinamide, or 4-HPR) is a semisynthetic retinoid that was initially developed as a low-dose chemopreventative agent.[1-3] Unlike other naturally occurring retinoids such as all-trans, 13-cis, and 9-cis retinoic acids, fenretinide does not induce systemic catabolism that interferes with the maintenance of effective plasma levels during long-term use. This characteristic, combined with the agent’s low toxicity and its ability to block aspects of carcinogenesis, provided the rationale for the development of fenretinide in lower doses as a chemoprevention agent for breast, prostate, and bladder cancer.

The role of adjuvant therapy following complete resection of node-positive (stage II/IIIA) non-small-cell lung cancer remains controversial. Five-year survival rates in pathologic stage II disease range from 30% to 50% and in resected stage IIIA disease from 10% to 30%. The majority of recurrences following surgery are distant metastases. This two-part review, which will conclude in the January 2002 issue, analyzes the role of adjuvant therapy in this setting, using an evidence-based approach and focusing primarily on randomized trials and meta-analyses. The key variables in evaluating these studies are elucidated, ranging from the extent of mediastinal, systemic, and "molecular" staging to the quality of the adjuvant treatments administered. Some of the potential flaws inherent in meta-analyses are reviewed. To date, there is no convincing evidence that any therapy consistently improves survival in the adjuvant setting. Postoperative radiotherapy has been associated with a significant improvement in local control, particularly in patients with pathologic N2 disease. Chemotherapy should be offered to patients in appropriate clinical trials, and active phase III trials are reviewed. Future strategies include novel chemotherapy, methods to reduce toxicity, the emerging role of neoadjuvant therapy, and the promise of new biologic agents. [ONCOLOGY 15:1549-1558, 2001]

CHICAGO-Concurrent chemo-radiotherapy and consolidation docetaxel (Taxotere) achieved an unprecedented 3-year survival rate of 40% in patients with stage IIIB non-small-cell lung cancer (NSCLC) in a phase II trial (SWOG 9504).

SAN FRANCISCO-A randomized phase III trial of three chemotherapy regimens in advanced non-small-cell lung cancer (NSCLC) confirmed platinum-containing combinations as the standard treatment, according to a presentation at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1228). The EORTC trial (08975) compared cisplatin (Platinol) and paclitaxel (Taxol) to gemcitabine (Gemzar) with either cisplatin or paclitaxel.

WASHINGTON-Abundant evidence links arsenic in drinking water to an increased risk of bladder and lung cancer and it is stronger than ever, according to a new report from the National Research Council (NRC), the research arm of the National Academy of Sciences.

SAN FRANCISCO-Early results with a regimen of gemcitabine (Gemzar), cisplatin (Platinol), and trastuzumab (Herceptin) in advanced non-small-cell lung cancer (NSCLC) patients overex-pressing HER-2 are encouraging, according to a presentation at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1307).

SAN FRANCISCO-Platinum-based chemotherapy with either gemcitabine (Gemzar) or paclitaxel (Taxol) caused fewer terminations of therapy for progressive disease or adverse events than the reference regimen of platinum with vinorelbine (Navelbine) in advanced non-small-cell lung cancer (NSCLC).

SAN FRANCISCO-Survival of patients with limited-stage small-cell lung cancer (SCLC) has doubled in the past 2 decades, largely because of advances in thoracic radiation, according to an analysis of more than 2 dozen randomized clinical trials and the SEER database. The findings were presented at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1264).

The Southwest Oncology Group (SWOG) is initiating a phase III trial (S0023) that will compare conventional chemoradiotherapy with consolidation docetaxel (Taxotere) followed by maintenance therapy with the investigational agent

EAST LANSING, Michigan-A study of 841 patients age 65 and older newly diagnosed with breast, colon, lung, or prostate cancer found three predictors of pain and fatigue: advanced stage, more comorbid conditions, and lung cancer, compared with breast cancer (the reference), according to researchers from Michigan State University.

SAN FRANCISCO-The biologic marker matrix metalloproteinase-9 (MMP-9) has been identified as an important new predictor of disease recurrence and poor outcome in non-small-cell lung cancer (NSCLC). It also offers some insight into the mechanisms by which NSCLC tumors grow and spread.

Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. Radiation doses that can be delivered, without causing severe damage to surrounding normal

SAN FRANCISCO-GVAX, an autologous cancer vaccine, demonstrated antitumor activity in non-small-cell lung cancer (NSCLC) patients in a phase I/II multicenter clinical trial. Interim data were presented at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 1019).

NASHVILLE, Tennessee-Irinotecan (Camptosar)/cisplatin (Platinol) combination therapy was significantly more effective and less toxic than standard etoposide (VePesid)/cisplatin in phase II trials, according to Alan B. Sandler, MD. The combination is now being tested in larger clinical studies. These confirmatory studies will use a 21-day cycle of irinotecan/cisplatin rather than the 28-day cycle used in preliminary studies.

NASHVILLE,Tennessee-"The significant discovery of the 1980s was that chemoradiotherapy is better than radiation alone for treating locally advanced non-small-cell lung cancer," stated Hak Choy, MD. "In the 1990s we learned that concurrent chemoradiotherapy is better than a sequential schedule. Our task now is to discover which drug regimen is best." Dr. Choy is professor and vice-chair of the Vanderbilt University Medical Center in Nashville, Tennessee.

NEW HAVEN, Connecticut-‘‘We’ve hit the wall in management of small- cell lung cancer (SCLC). We need a paradigm shift," John R. Murren, MD, stated. He is associate professor of medicine at Yale University School of Medicine in New Haven, Connecticut.

CHICAGO-Preliminary results of a phase I trial of induction chemotherapy followed by chemoradiotherapy with irinotecan (Camptosar), paclitaxel (Taxol), and carboplatin (Paraplatin) showed that this approach is feasible and active in stage III non-small-cell lung cancer (NSCLC), reported Ann M. Mauer, MD. The dose-limiting toxicity when combining these three drugs with concurrent chest radiotherapy was neutropenia, and weekly delivery of the regimen was not feasible at the originally planned doses. Dr. Mauer is assistant professor of medicine at the University of Chicago Pritzker School of Medicine in Chicago, Illinois.

A subcommittee of the NCI’s Board of Scientific Advisors is considering whether to recommend that the NCI undertake a

HOUSTON-‘‘We appear to be approaching a ceiling for benefits of cytotoxic chemotherapy in advanced non-small-cell lung cancer (NSCLC). All recent randomized studies have had similar results, and there has been no clear efficacy benefit from nonplatinum combinations or triplets. Certainly for advanced disease and even for early disease, where metastases kill most patients, a paradigm shift is needed, and that shift will probably be to targeted therapy that works against specific biologic pathways," said Roy S. Herbst, MD, PhD. Dr. Herbst is assistant professor of medicine and chief of the Section of Thoracic Oncology at the University of Texas M.D. Anderson Cancer Center in Houston, Texas.

BMS-247550 is a methyl, semi-synthetic analog of the natural product epothilone B. Provided to the National Cancer Institute (NCI) by Bristol-Myers Squibb, BMS-247550 was chosen for clinical development because it demonstrated

TAMPA, Florida-Irinotecan (Camptosar)/gemcitabine (Gemzar) combinations are being studied in two lung cancer trials. Caio Max S. Rocha Lima, MD, assistant professor of medicine at the University of South Florida’s H. Lee Moffitt Cancer Center in Tampa, Florida, presented overviews of the protocols.

PHILADELPHIA-Concurrent chemoradiotherapy seems likely to become standard therapy for treating locally advanced lung cancer. That would make preventing radiation-induced esophagitis even more important, according to Maria Werner-Wasik, MD.

ST LOUIS-In a small phase II study, amifostine (Ethyol) provided little advantage in esophageal protection for patients with limited-stage small-cell lung cancer (SCLC) treated with chemotherapy and twice-daily radiation. Results of the trial were reported by Todd H. Wasserman, MD. Dr. Wasserman is professor of radiation oncology and clinical chief, Department of Radiation Oncology, Washington University Medical Center, St. Louis.

HOUSTON-Amifostine (Ethyol) can reduce the risk of acute pneumonitis and severe esophagitis associated with concurrent radiation and chemotherapy administered to patients with advanced non-small-cell lung cancer (NSCLC). Results of a phase III study were reported by Ritsuko Komaki, MD, professor of radiation oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

PIREAUS, Greece-In advanced-stage lung cancer, radiation therapy provides effective local-regional control but requires irradiation of large tissue volumes and high total tumor doses. "Bolus tumor doses higher than 60 Gy produce better local tumor control but more toxicity," Dosia Antonadou, MD, explained.

According to phase III trial data presented at the recent meeting of the American Society of Clinical Oncology (ASCO)

Given the well-established role of angiogenesis (or new blood vessel formation) in tumor growth and metastasis, antiangiogenic therapy, a concept first proposed by Dr. Judah Folkman,[1] has become increasingly recognized as a promising

CHICAGO-Multiple independent laboratories have verified the presence of simian virus 40 (SV40) DNA and proteins in human mesotheliomas, brain tumors, and bone tumors, using a variety of methods of detection. This was the consensus reached by a panel of scientists at an international conference hosted by the University of Chicago.

BETHESDA, Md-Enrollment has begun in a trial of Neovastat (Aeterna Laboratories), also known as AE-941, to test the Canadian-produced shark cartilage extract in patients with unresectable stages IIIA and IIIB non-small-cell lung cancer (NSCLC) who are undergoing induction chemotherapy and radiation therapy.

SAN FRANCISCO-The Mayo Lung Project has been widely interpreted to be negative because it failed to demonstrate a significant reduction in lung cancer mortality among persons randomized to screening chest x-rays. But a rigorous new analysis, with mortality adjusted for cancer incidence, suggests otherwise: that mortality from non-small-cell lung cancer (NSCLC) is reduced by chest x-ray screening and that public policy recommendations against screening deserve to be reconsidered.