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4'-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) is a new, second generation platinum analog which had demonstrated in vitro activity in L1210 cell lines resistant to cisplatin and had less nephrotoxicity than did cisplatin in preclinical animal testing. A Phase I trial with this agent has been performed in 45 patients with advanced refractory cancers. Nine dosage levels, ranging from 40 to 800 mg/sq m, were studied. Major toxicities seen were myelosuppression, nephrotoxicity (which was generally mild), nausea and vomiting (which was quantitatively less than that seen with cis-platin), allergic reactions, and a peripheral neuropathy. The dose-limiting toxicity was thrombocytopenia. Pharmacokinetics performed at three dosage levels indicates that 4'-carboxyphthalato-(1,2-diaminocyclohexane)platinum(II) has a long t1/2 of 20 to 30 hr (total platinum) and is only partially excreted in the urine and that a high proportion of the drug is nonfilterable within 30 to 60 min of administration. Therapeutic responses were seen in nasopharyngeal carcinoma, adenocarcinoma of the cervix, and lung and gastric cancer. As a starting dose for Phase II studies, which are planned for patients with ovarian, testicular, lung, gastric, and esophageal cancers, 640 mg/sq m given every 3 to 4 weeks is recommended.
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
October 1984,
American journal of clinical oncology,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
April 1985,
Cancer treatment reports,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
January 1986,
Anticancer research,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
January 1981,
Cancer clinical trials,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
July 1990,
Cancer research,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
March 1974,
Research communications in chemical pathology and pharmacology,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
January 1980,
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
January 1986,
Cancer chemotherapy and pharmacology,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
January 1986,
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
D P Kelsen, and
H Scher, and
N Alcock, and
B Leyland-Jones, and
A Donner, and
L Williams, and
G Greene, and
J H Burchenal, and
C Tan, and
F S Philips, and
C W Young
April 1987,
Journal of medicinal chemistry,
