NEW YORKA trial is being launched to explore whether lengthening the
platinum-free interval will affect recurrent ovarian cancer outcomes, William
P. McGuire, MD, medical director, oncology, Franklin Square Hospital Center,
Baltimore, announced at the Mount Sinai School of Medicine Chemotherapy
Foundation Symposium XX.
Data laying the theoretical basis for the project, Dr. McGuire said,
include studies in which response rates rose with lengthened platinum-free
intervals. If the platinum-free interval is less than 5 months, he noted,
"there is a very low chance of response." If the interval is longer than 2
years, in at least one study, he said, the response rate was 59%, "not
dissimilar from what you would expect if you were treating a chemonaïve
patient." In contrast, when the interval was 6 to 12 months, the response
rate was 27% and when the interval was 12 to 24 months, the response rate was
- Patients’ response to first-line platinum therapy, Dr. McGuire
stressed, also affects second-line or salvage efforts. He defined four
- Platinum-refractory patients, he noted, do not respond to primary
therapy or have an incomplete response. For these patients, who usually die
within 12 to 18 months, he recommended trials of investigational drugs.
- Platinum-resistant patients have a limited response to primary therapy
and tumor recurrence within 6 months. These patients, too, he said, are not
likely to benefit from a second round of platinum therapy.
- Platinum-sensitive patients have a complete response to primary therapy
and do not have recurrent disease until at least 6 months after
discontinuation of that treatment.
- Very-platinum-sensitive patients have a complete response to primary
therapy and tumor recurrence 18 to 24 months after finishing the initial
The majority of ovarian cancer patients, Dr. McGuire said, are platinum
sensitive and have platinum-free intervals of 6 to 18 months before disease
recurrence. Whether the platinum-free interval can be extended and improve
survival remains unknown, he said.
"Does it make sense," he asked, "to withhold platinum therapy in that
patient who has a 6 to 18 month platinum-free interval now that we have
multiple drugs that have similar response rates to platinum in this patient
The return of platinum sensitivity over time is not fully understood, he
noted, "but we do know that a lot of platinum resistance is due to
upregulation of excision repair enzymes, and, at least in vitro, if you take
platinum out of the cell culture, those excision repair enzymes actually
In platinum-sensitive patients with recurrent ovarian cancer, he observed,
response rates with nonplatinum agents are comparable to those with platinums
in the same setting. In a study by the Gynecologic Oncology Group in which
the median platinum-free interval was 9.6 months, Dr. McGuire noted, the
response rate to the standard dose of topotecan (Hycamtin) was 33%.
"Alternate agents may, in fact, allow a further increase in the platinum-free
interval," he said, "and may improve response to platinums later."
Some nonplatinum agents, however, carry a risk of cumulative toxicity, Dr.
McGuire cautioned. Weekly doses of paclitaxel (Taxol) at 80 to 100 mg/m2 have
been associated with cumulative peripheral neurotoxicity in more than 25% of
patients, he noted. Among the few agents that have not been shown to increase
the adverse event profile, he noted, are topotecan and gemcitabine (Gemzar).