Irinotecan and Other Agents in the Management of Mul
Published on Psychiatric Times
(http://www.psychiatrictimes.com)
Irinotecan and Other Agents in the Management of Multiple
Tumor Types
December 04, 2004
By Jaffer A. Ajani, MD [1]
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.
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
Page 1 of 2
Irinotecan and Other Agents in the Management of Mul
Published on Psychiatric Times
(http://www.psychiatrictimes.com)
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.
Source URL:
http://www.psychiatrictimes.com/oncology-journal/irinotecan-and-other-agents-management-multipl
e-tumor-types
Links:
[1] http://www.psychiatrictimes.com/authors/jaffer-ajani-md
Page 2 of 2