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Irinotecan and Other Agents in New Combinations and Other Tumor Types

Irinotecan and Other Agents in New Combinations and Other Tumor Types

The 4th Investigators’ Workshop sponsored by The
University of Texas M. D. Anderson Cancer Center

was held on July 25-29, 2001,
in Colorado Springs, Colorado. The purpose of these annual workshops has been to
review the latest data on new agents, with a particular focus on the broadly
used agent irinotecan (CPT-11, Camptosar).

Investigators from around the world were invited to present current research.
The forums were highly interactive and frank, thus allowing stimulation of new
ideas and directions. The meetings were more like a workshop rather than
didactic sessions. Six separate scientific sessions were held, and the
respective sessions covered colorectal carcinoma, upper
gastrointestinal/genitourinary carcinoma, lung carcinoma, and new combinations
and other tumor types.

In addition to stimulating research, another purpose of these workshops is to
develop enduring material for wider distribution to those who did not attend.
Thus, four publications are intended. This third volume is devoted to new
combinations and other tumor types. The two previous volumes focused on
colorectal cancers and upper gastrointestinal/genitourinary carcinomas. The
fourth and final volume will be devoted to lung malignancies.

New Agents in Antiangiogenesis

In this volume, Jordan Berlin reviews preclinical and clinical data leading
to the current trials of two new agents that inhibit pathways associated with
tumor angiogenesis. Standard first-line therapy for patients with metastatic
colorectal cancer consists of IFL (fluorouracil, leucovorin, and irinotecan).
Bevacizumab (Avastin), a recombinant humanized monoclonal antibody to vascular
endothelial growth factor (VEGF), is being assessed in a randomized trial of IFL
with or without bevacizumab. The tyrosine kinase inhibitor SU5416, targeted
against the Flk-1 receptor for VEGF, is being tested in a phase I/II trial
combined with IFL.

Irinotecan and Epirubicin in Advanced Cancer

John Marshall and coworkers present a phase I clinical study that represents
an investigation of the first combination of irinotecan and epirubicin (Ellence)
in patents with advanced cancer. These drugs are significant chemotherapeutic
agents that are used in the management of many different cancers. Each agent
works through the inhibition of topoisomerases, and inhibition of topoisomerases
I and II may result in significant clinical synergy. Evidence of clinical
activity was observed, including activity in two typically resistant tumor
types. There was significant myelosuppression in the original cohort that
required a modification in the initial dose-escalation scheme, and accrual to
these lower doses is ongoing.

Irinotecan and Mitomycin

Other agents, such as mitomycin (Mutamycin), also possess significant
single-agent activity against several tumor types, and mitomycin activates
topoisomerase I, the cellular target of irinotecan. Miguel Villalona-Calero and
Jill Kolesar
discuss data from a phase I dose-escalation study of irinotecan and
mitomycin in 37 evaluable patients with solid tumors. The response rate was 49%,
including 2 complete responses, 5 partial responses, 10 minor responses, and a
CA 19-9 tumor marker response. These encouraging data provided the rationale for
ongoing phase II clinical trials in breast and esophageal/gastroesophageal
junction adenocarcinomas at the recommended doses and schedule.

Irinotecan in Non-Hodgkin’s Lymphomas

Andreas Sarris et al investigate the activity of irinotecan in relapsed or
refractory non-Hodgkin’s lymphomas (NHLs). The every-21-days irinotecan
schedule is attractive for the treatment of lymphoma, because irinotecan may be
combined with other myelosuppressive drugs that are active in lymphoma—which
are also usually given every 21 days—and can be supported by hematopoietic
growth factors to minimize or prevent neutropenia. In 32 evaluable patients,
response rates were 43% for 7 indolent, 0% for 3 mantle cell, 44% for 18
relapsed aggressive, and 20% for 5 refractory aggressive NHLs. Grade 3/4
toxicities included myelosuppression, neutropenic fever, and diarrhea. Accrual
is continuing in this ongoing study.

EIAEDs and the Pharmacokinetics of Irinotecan

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