Irinotecan and Other Agents in the Management of Multiple Tumor Types

The 6th University of Texas M. D. Anderson Cancer Center Investigators' Workshop was held on July 16-20, 2003, in Amelia Island, Florida. The purpose of these annual workshops has been to review the latest data on new agents, with a particular emphasis on the broadly used agent irinotecan (Camptosar), and also novel regimens or agents. Investigators from around the world are invited to present current research. The forums are highly interactive and frank, thus allowing stimulation of new ideas, directions, and potential investigative collaborations. Also, the use of case studies and poster sessions provided another avenue of interaction among meeting faculty and participants. Six separate scientific sessions were held, and the respective sessions covered lung carcinoma, gastrointestinal cancer, breast malignancy, novel therapies/new combinations, other tumor types, as well as highlights from the 39th annual meeting of the American Society of Clinical Oncology. In addition to stimulating research, another purpose of these workshops is developing enduring material for wider distribution to those who did not attend this workshop. In this combined volume, selected presentations from the various sessions are included. Lung Cancer Treatment Options
Overexpression of cyclooxygenase-2 (COX-2) is frequently present in lung cancer, and it may play a significant role in carcinogenesis, invasion, and metastasis. Moreover, it is associated with shortened survival in early-stage adenocarcinoma. Elizabeth Gore presents the rationale for COX-2 inhibitors in lung cancer and presents data from a phase II study of concurrent celecoxib (Celebrex) and thoracic irradiation in patients with non-small-cell lung cancer (NSCLC). William Read et al present a phase II trial of the combination of irinotecan and carboplatin (Paraplatin) in NSCLC. It is thought that carboplatin is better tolerated than and equally efficacious as cisplatin in this arena. Gastrointestinal Cancer
In esophageal cancer, the limited efficacy and toxicity of conventional fluorouracil (5-FU)/cisplatin-based chemotherapy has prompted the evaluation of newer agents and combinations. Ramaswamy Govindan et al present a phase II study of cisplatin, 5-FU, celecoxib, and radiation therapy in patients with resectable disease. David Ilson presents data from a multicenter phase II trial of weekly irinotecan and cisplatin in advanced esophageal cancer. The combination of irinotecan with 5-FU/leucovorin (IFL) has consistently improved survival and response rates in comparison to 5-FU/leucovorin alone in patients with colorectal cancer. Continuing efforts to improve its toxicity profile, while retaining or improving upon the therapeutic outcomes, are ongoing. Jimmy Hwang reviews the various combinations of irinotecan with 5-FU/leucovorin, and discusses data from his group's efforts to improve the therapeutic index of weekly IFL by incorporating a break after the second week of therapy, prior to resuming IFL. Targeting the epidermal growth factor receptor (EGFR) in colorectal cancer is another important therapeutic tool, and a monoclonal antibody against the extracellular domain of EGFR (cetuximab [Erbitux]) has recently been approved for the treatment of EGFR-positive metastatic disease refractory to irinotecan-based therapy. Jeffrey Meyerhardt et al discuss the role of targeted agents against EGFR, including other monoclonal antibodies as well as inhibitors of the intracellular tyrosine kinase domain. Weijing Sun and coworkers present data from phase I combined-modality studies of concurrent radiation therapy with continuous infusion 5-FU and epirubicin (Ellence) with either cisplatin or irinotecan for locally advanced upper gastrointestinal adenocarcinoma. Allan Lipton et al describe data from a trial that investigated whether the addition of a COX-2 inhibitor to chemotherapy was beneficial in patients with unresectable pancreatic cancer, a malignancy with few therapeutic options and a dismal prognosis. (COX-2 expression is increased in most human pancreatic cancers.) Patients received gemcitabine (Gemzar), irinotecan, and celecoxib, and achieved pain relief, improvement in performance status, and decreases in CA 19-9 and carcinoembryonic antigen levels. Carlos Becerra concludes the gastrointestinal section with data from a phase I study with irinotecan, epirubicin, and the novel agent capecitabine in patients with metastatic adenocarcinomas. He reports the tolerability and efficacy of the regimen, without pharmacokinetic interaction. Combined-Modality Therapy in Rectal Cancer
The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined-modality therapy (T3 and/or N1/2 tumors) and preoperative combined-modality therapy followed by surgery and postoperative chemotherapy (ultrasound T3 or clinical T4). Bruce Minsky reviews phase I/II trials investigating new chemotherapeutic agents in combination with pelvic radiation therapy, especially in the preoperative setting, and points out the considerable interest in integrating irinotecan into preoperative combined- modality therapy regimens. Based on these data, the recommended regimen for patients who receive irinotecan-based combined-modality therapy is continuous infusion 5-FU, irinotecan, and pelvic radiation. Breast Cancer Treatment Approaches
Adjuvant chemotherapy is beneficial in patients with breast cancer, with anthracycline-containing regimens being more effective than non-anthracyclinecontaining ones. Jacques Bonneterre presents a follow-up analysis of the French Adjuvant Study Group trial comparing FEC100 and FEC50 (5-FU/epirubicin/ cyclophosphamide [Cytoxan, Neosar]) in patients with node-positive breast cancer. After a median follow-up of 10 years, the benefit/risk ratio of the FEC100 regimen in patients with positive axillary nodes was strongly positive, and a cost analysis showed that the relatively low cost per year of life saved was around 1,000 euros. Michael Untch et al report cardiotoxicity and efficacy data from a multicenter phase II study of the combination of epirubicin/cyclophosphamide plus a humanized monoclonal antibody specific for HER2/neu (trastuzumab [Herceptin]) in breast cancer treatment. Conclusion
In conclusion, I believe that the data presented at the University of Texas M. D. Anderson Cancer Center Investigators' Workshop provided new insights and perspectives, trends, and practices in various areas of oncology. I hope the reader will find the information presented herein to be relevant, stimulating, and useful in designing new trials.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.