Phase I clinical trial of ormaplatin (tetraplatin, NSC 363812).
Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose level showed a Cpmax of 163 ng/ml and a t1/2 of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.
Hematology-Oncology Service, Brooke Army Medical Center, Fort Sam Houston, TX 78234-6200.
T J
TJ
O'Rourke
G R
GR
Weiss
P
P
New
H A
HA
Burris
G
G
Rodriguez
J
J
Eckhardt
J
J
Hardy
J G
JG
Kuhn
S
S
Fields
G M
GM
Clark
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count / Q000187:drug effects; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D013054:Spectrophotometry, Atomic; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C049777:ormaplatin