Rl. Theriault et al., A PHASE-II STUDY OF CI-973 LATO(2-)](2-METHYL-1,4-BUTANEDIAMINE-N,N')PLATINUM IN PATIENTS WITH REFRACTORY ADVANCED BREAST-CANCER, Cancer chemotherapy and pharmacology, 38(3), 1996, pp. 289-291
CI-973 is a water-soluble platinum diamine complex whose antitumor act
ivity is greater than that of cisplatin in some murine tumors. It has
shown activity against cisplatin-resistant tumors. This phase II trial
had the objectives of determining the therapeutic efficacy of CI-973
in patients with metastatic breast cancer who had been treated with on
e prior chemotherapy regimen, and of further defining the toxicity of
the agent and the reversibility of its toxicity. CI-973 was administer
ed as an intravenous infusion over 30 min with no prehydration or anti
emetic programs. Treatment cycles were repeated at 21-day intervals. P
atients with histologically confirmed metastatic breast cancer, measur
able disease, and good performance status who had received only one pr
ior chemotherapy regimen for metastatic disease were eligible for trea
tment. Adequate hematologic, renal, and hepatic function were required
. A total of 26 patients received a median of two courses of CI-973 (r
ange, 1-18 courses). Hematologic toxicity was severe: nearly all patie
nts experienced granulecytopenia with granulocyte counts of 0 at all d
ose levels. Nevertheless, neutropenic fever and documented systemic in
fection were uncommon, and there were no hospitalizations for neutrope
nic fever or infection. Visceral disease dominated in this patient gro
up. Of the 26 patients, 14 had visceral disease, 6 had bone or bone ma
rrow disease, and 6 had skin, soft-tissue, or lymphnode disease. Of th
e 26 patients treated, 25 were evaluable for response. There were two
partial remissions, one in liver and one in bone, and three minor resp
onses, for a response rate of 8%. Nonhematologic toxic effects were mi
ld and consisted of nausea and vomiting, fatigue, minimum peripheral p
aresthesia, and hypomagnesemia. Further study of CI-973 at the dose an
d schedule used in this study is not warranted. Because this agent had
no significant extramedullary toxicity, intensification of the dose o
f CI-973 with concomitant administration of colony-stimulating factors
has the potential to improve response in this patient population.