Gastrointestinal Cancer

Since its development in 1957, fluorouracil (5-FU) has been the central component in the treatment of colorectal cancer. Over the past several decades, innumerable permutations of fluorouracil biomodulation have been studied. Indeed, rarely has a drug been so well understood in terms of its mechanisms and metabolism, and rarely has such an understanding been so extensively exploited in clinical strategies. But despite these efforts, overall progress in the management of advanced colorectal cancer has been modest.

Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) are active cytotoxic drugs against pancreatic cancer. Preclinical data evaluating the combination of gemcitabine and irinotecan suggest dose-dependent synergistic

The treatment of advanced colorectal cancer over the past 4 decades has required the use of intravenous chemotherapy, most typically fluorouracil (5-FU). The possibility of providing

As the chemotherapy horizons have expanded in colorectal cancer with development of oxaliplatin (Eloxatin) and irinotecan (CPT-11, Camptosar), so too have our approaches to therapy. Numerous immunotherapy and gene

NEW YORK-Although no complete responses occurred in patients with advanced pancreatic cancer in a study of DX-8951F (exatecan mesylate, Daiichi Pharmaceuticals), those who were treatment-naïve survived longer than usual, and stable disease was observed in 39%, Eileen M. O’Reilly, MD, reported at the Chemotherapy Foundation Symposium XVIII.

NEW YORK-Because pivotal studies failed to show a survival advantage, oxaliplatin did not receive FDA approval as first-line therapy of metastatic colorectal cancer last year.

In the largest prospective study of cigarette smoking and colorectal cancer mortality, researchers from the American Cancer Society report finding strong evidence that cancers of the colon and rectum are, in part, smoking related.

Capecitabine (Xeloda) is the first orally available fluoropyrimidine approved for use in patients with cancer. It was initially approved for use in metastatic breast cancer, but significant data also support its use in the management

Randomized studies have tested a variety of strategies to improve the activity of 5-fluorouracil (5-FU) in colorectal cancer patients. Results from 14 randomized trials comparing 5-FU administered via intravenous ( IV) bolus either

Significant emphasis has been placed recently on designing more effective fluorouracil (5-FU)-based combination protocols for gastrointestinal cancer. Promising results were seen with 5-FU/leucovorin in combination with

NEW YORK-An irinotecan (Camptosar) plus gemcitabine (Gemzar) combination known as IrinoGem was associated with low toxicity, median survival of 6 months, and a 1-year survival rate of 27%, according to results from a phase II study presented at the Chemotherapy Foundation Symposium XVIII.

BOSTON-Neoadjuvant therapy for adenocarcinoma of the rectum is well tolerated and can produce substantial downstaging and high curative resection rates, according to a retrospective study presented at the American Society of Colon and Rectal Surgeons (ASCRS) annual meeting. The manuscript of the study has been accepted for publication in Diseases of the Colon and Rectum.

NEW YORK-The combination of oxaliplatin (investigational) and irinotecan (Camptosar) as front-line treatment for colorectal cancer is feasible and potentially synergistic, preliminary data from an M.D. Anderson Cancer Center phase I/II trial suggests.

Ateam of European researchers recently reported that the addition of oxaliplatin to the standard regimen for advanced colorectal cancer of fluorouracil (5-FU) and leucovorin doubled the response to therapy and significantly prolonged progression-free survival, compared to leucovorin and 5-FU alone.

Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of the plant alkaloid camptothecin. This review will focus on the potential use of irinotecan in combination with fluorouracil (5-FU) in the preoperative combined-modality treatment of advanced rectal cancer.

Fluorouracil (5-FU) has remained the standard therapy for the treatment of advanced colorectal cancer for over 40 years. Unfortunately, only a minority of patients experience objective clinical response.

Synergy with no overlapping toxicities has been demonstrated for the combination of irinotecan ( Camptosar, CPT-11) and gemcitabine (Gemzar) in vitro. Results of a single-institution phase I study in which patients with

Irinotecan (Camptosar) is a topoisomerase I inhibitor with demonstrated antitumor activity against a wide variety of malignancies. Phase II studies have shown that this agent has significant single-agent activity against both chemotherapy-naive and fluorouracil (5-FU)-refractory colorectal cancer. Phase III studies now indicate that irinotecan/5-FU/leucovorin combinations have antitumor activity superior to standard 5-FU/leucovorin regimens alone. These irinotecan-based combinations are now entering clinical trials for the adjuvant treatment of resected stage III colon cancer. It is hypothesized that the superior antitumor activity of these irinotecan-based combinations seen in the metastatic setting will translate into improved survival and increased cure rates in these earlier-stage patients. [ONCOLOGY 14(Suppl 14):47-50, 2000]

Two randomized phase III trials with irinotecan as second-line treatment of metastatic colorectal cancer have shown that irinotecan (CPT-11, Camptosar) significantly improves survival when compared with best supportive care or continuous infusion of fluorouracil (5-FU) after failure of 5-FU.

Fifteen patients with metastatic colorectal cancer were treated with irinotecan (CPT-11, Camptosar) at 300 to 350 mg/m2 every 21 days and thalidomide (Thalomid) at 400 mg/d. Of the 15 patients, 11 were in a pilot study and 4

HOUSTON-Colorectal cancer mortality has declined slightly in the last 10 years, and the decrease appears to be accelerating. This decline is due in large part to screening and early detection, said Patrick M. Lynch, MD, associate professor of medicine, University of Texas M.D. Anderson Cancer Center.

PHILADELPHIA-Pancreatic cancer patients usually lose 25% of their body mass within 4 months of diagnosis and die within 6 months. But early work from Scotland on supplementation with eicosapentaenoic acid (EPA) seems to suggest that the fatty acid may stabilize weight and add months to the lives of pancreatic cancer patients.

One of the more promising chemotherapeutic agents for patients with metastatic colorectal cancer is oxaliplatin (Eloxatin), a third-generation platinum derivative with a unique mechanism of action. Preclinical studies

The current standard of care for patients with stage T3 rectal cancer is adjuvant combined-modality treatment with radiation and fluorouracil (5-FU)-based chemotherapy. Although data from randomized phase III trials comparing

Oxaliplatin (Eloxatin) has demonstrated significant activity in a variety of tumor types in addition to colorectal cancer. Several studies have reported on the effectiveness of oxaliplatin as single-agent treatment or in

No adequate second- or third-line therapy is available in the United States for patients with metastatic colorectal cancer and disease progression following treatment with fluorouracil (5-FU)-based therapy and an irinotecan (CPT-

Colorectal cancer is one of the leading causes of cancer death. The mainstay of chemotherapy in colorectal cancer patients for the past 40 years has been fluorouracil (5-FU). Oxaliplatin (Eloxatin) is a novel platinum compound with promising activity in colorectal cancer. As a single agent, oxaliplatin has produced response rates of 12% to 24% in patients with previously untreated advanced colorectal cancer, and 10% to 11% in patients with relapsed or refractory advanced colorectal cancer. In phase II trials, oxaliplatin combined with 5-FU, with or without leucovorin, was associated with response rates of 60% and higher when used as front-line therapy, and when used in patients with relapsed or refractory advanced colorectal cancer, response rates ranged from 25% to 50%. In the front-line setting, two randomized trials of 5-FU and leucovorin, with or without oxaliplatin, demonstrated that the addition of oxaliplatin significantly increases response rate and time to tumor progression, but not survival, over 5-FU plus leucovorin alone. The reasons for this discrepancy are unclear, and several possibilities are being considered. Additional phase III trials are underway to clarify the contribution of oxaliplatin in the treatment of patients with locally advanced and metastatic colorectal cancer. [ONCOLOGY 14(Suppl 11):9-14, 2000]

Therapy of hepatocellular carcinoma in cirrhotic patients is challenging. Liver dysfunction, portal hypertension, third spacing, thrombocytopenia, and neutropenia limit the choice of chemotherapeutic agents. However, the abundant vascularity of hepatocellular carcinoma presents an attractive target for antiangiogenic therapy, potentially tolerable even in cirrhotics.

BOSTON-Despite the pessimism of many experts, patients can benefit from surgery for locoregional recurrence of colorectal cancer, according to a 12-year retrospective study presented by Julio Garcia-Aguilar, MD, PhD, at the American Society of Colon and Rectal Surgeons (ASCRS) annual meeting.

BOSTON-A hybrid approach mixing laparoscopic and open procedures in surgery for rectal cancer may allow patients a faster recovery, Richard L. Whelan, MD, said at the American Society of Colon and Rectal Surgeons annual meeting. The approach uses laparoscopic methods for splenic flexure takedown in the area near the diaphragm at the start of the operation and switches to open surgery for removal of the cancer from the rectum.