GAITHERSBURG, Md--By a unanimous vote, the FDA's Oncologic Drugs
Advisory Committee (ODAC) recommended accelerated approval of
Pharmacia & Upjohn's Camptosar (irinotecan hydrochloride injection),
and the FDA responded by giving its ok to the drug 28 hours later.
Camptosar, the first new agent approved for colon cancer in 40
years, is indicated for metastatic carcinoma of the colon or rectum
that has recurred or progressed following fluorouracil (5-FU)-based
Camptosar, also known as CPT-11, is converted in the body to SN-38,
a potent modifier of topoisomerase I, an enzyme responsible for
DNA incision and relaxation prior to cell replication. SN-38 stabilizes
the enzyme with DNA and this "leads to a double-stranded
DNA break that results in cell death," explained Langdon
Miller, MD, of Pharmacia & Upjohn. "In essence, SN-38
converts topoisomerase I into a cellular toxin."
Daniel D. Von Hoff, MD, of the University of Texas Health Science
Center, San Antonio, noted that physicians in the United States
will diagnose more than 133,000 colorectal cancers and the disease
will kill 54,000 people in 1996. Only about 12% of patients whose
initial tumor metastasizes live more than 2 years.
"There has been no effective single-agent therapy for patients
with advanced colorectal cancer after they have received prior
treatment with 5-FU or a 5-FU containing regime," Dr. Von
Henry C. Pitot, MD, of the Mayo Clinic, reviewed three pivotal
Camptosar trials with a total of 304 previously treated colorectal
patients. (Upjohn began a phase III study in May 1996). "The
efficacy endpoint was objective complete or partial tumor response,"
Thirty-nine patients (12.8%) responded, 2 with a complete response
and 37 with partial responses, Dr. Pitot said. "Nearly 40%
to 65% of patients had stable disease as their best response,
with some patients experiencing substantial or protracted reduction
in tumor burden," he added. Time to progression was about
6 months for those with stable disease and median survival was
9 months with a range of up to nearly 3 years.