Abstract | PURPOSE:
Edatrexate (10-Edam) is a methotrexate analog with improved intracellular transport, polyglutamation, and antitumor activity compared to the parent compound. Edatrexate shows schedule-dependent synergism with platinum compounds in preclinical studies. We performed a phase I trial to determine toxicities and establish the maximum tolerated dose (MTD) of edatrexate in combination with carboplatin. Based on the short initial plasma half-life of edatrexate, prophylactic ice chip cryotherapy was used to reduce the severity of mucositis. PATIENTS AND METHODS: Forty-six chemotherapy-naive patients with advanced solid tumors were treated. Edatrexate was given weekly for 5 doses (50% on day 8), and then every other week, followed by carboplatin at a fixed dose of 350 mg/m2 on day 1 and then every 4 weeks for 8 cycles. Edatrexate dose was increased at increments of 10 mg/m2/dose level beginning at 60 mg/m2/week (range 60-120 mg/m2). RESULTS: CONCLUSIONS: 1 ) This phase I study demonstrated the safety and tolerability of this edatrexate and carboplatin combination. 2) Dose-limiting mucositis did not occur allowing escalation of edatrexate dose above levels previously achieved with this edatrexate dose schedule. This was most likely a result of prophylactic ice chip cryotherapy. 3) An edatrexate dose of 110 mg/m2 with ice chip cryotherapy is recommended for Phase II trials of this combination.
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Authors | M J Edelman, D R Gandara, E A Perez, D Lau, I Lauder, C Turrell, M Uhrich, F Meyers |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 16
Issue 1
Pg. 69-75
( 1998)
ISSN: 0167-6997 [Print] United States |
PMID | 9740546
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carboplatin
- edatrexate
- Aminopterin
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Topics |
- Adult
- Aged
- Aminopterin
(administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
- Anemia
(chemically induced)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Carboplatin
(administration & dosage, adverse effects, therapeutic use)
- Cryotherapy
- Exanthema
(chemically induced)
- Female
- Humans
- Leukopenia
(chemically induced)
- Male
- Middle Aged
- Mucous Membrane
(drug effects)
- Neoplasms
(drug therapy)
- Vomiting
(chemically induced)
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