of data from multiple phase II
trials with novel agents cetuximab(Drug information on cetuximab) (Erbitux)
and erlotinib (OSI-774, Tarceva)
have concluded that patients who
developed an acne-like rash lived longer
than those who did not, and that patients with more severe rash lived
longer than patients with mild rash
In presenting their analyses at the
39th Annual Meeting of the American
Society of Clinical Oncology (ASCO)
(abstracts 786 and 817), the investigators
suggested that rash could be a
biomarker for response to HER1/
epidermal growth factor receptor inhibitors
(HER1/EGFR). Rash also was
identified as a predictor of response to gefitinib(Drug information on gefitinib) (ZD1839, Iressa), a third
agent that targets EGFR (J ClinOncol
The big question is whether the
observation will prove clinically useful.
Both groups of researchers speculated
that the optimal dose of HER1/
EGFR inhibitors could be linked to an
optimal degree of rash in each patient,
but they cautioned that the rash might
be a surrogate for another factor involved
in the response.
"It could mean that a strategy for
improving the effectiveness of the drug
could be to dose to a certain level of
rash... in order to escalate to a degree
of side effect that will be commensurate
with a higher degree of activity,"
said Leonard B. Saltz, MD, associate
attending physician, Memorial Sloan-
Kettering Cancer Center.
"An alternative hypothesis would
be that patients have particular polymorphisms
of the epidermal growth
factor receptor that make them more
vulnerable to toxicity and their tumors
more vulnerable to the attack by
this particular drug," Dr. Saltz continued.
"We really don't know if this
observation will have a therapeutic
meaning or not," Dr. Saltz said.
Gary M. Clark, PhD, senior director
of biostatistics and data management
of OSI Pharmaceuticals, Inc.,
compared the rash to tumor flares experienced
by breast cancer patients treated with tamoxifen(Drug information on tamoxifen) in the early
1980s. Some women asked to be taken
off the then-new drug because of pain
and vaginal dryness, but it turned out
to be a sign the drug was working, said
Dr. Clark, lead investigator of the
"The question, of course, is can we
do anything about this? Can we take
advantage of it?" Dr. Clark said. "Is it
possible to increase the dose in some
patients and achieve a better clinical
outcome?" He said that OSI has already
started a dose-to-rash study.
Review of Previous Trials
Dr. Saltz and Dr. Clark each mined
data from previously reported phase
II trials. ImClone Systems Incorporated,
Somerville, New Jersey, developer
of cetuximab with Bristol-Myers
Squibb Oncology, participated in the
Dr. Saltz reviewed trials evaluating
- with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar) in 120 patients with colorectal cancer;
- alone in 57 colorectal cancer patients; with cisplatin(Drug information on cisplatin) in 79 patients with squamous cell cancer of the head and neck; and
- with gemcitabine(Drug information on gemcitabine) (Gemzar) in 41 pancreatic cancer patients.
- Among 57 patients with refractory non-small-cell lung cancer (NSCLC), 75% developed rash.
- Among 115 patients with advanced squamous cell cancer of the head and neck, 70% developed rash.
- Among 34 patients with advanced ovarian cancer, 82% developed rash.