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`A PHASE I AND PHARMACOKINETIC (PK) STUDY
`OF THE MULTITARGETED ANTIFOL (MTA)
`LY231514 WITH FOLIC ACID (Meeting abstract).
`
` Print this page
`
`
`
`Sub-category:
`Other
`
`Category:
`Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
`
`Meeting:
`1998 ASCO Annual Meeting
`
`Abstract No:
`866
`
`Author(s):
`L Hammond, M Villalona-Calero, SG Eckhardt, R Drengler, C Aylesworth, T Johnson, M Hidalgo, G Rodriguez, S
`Diab, P Monroe, D Thornton, Hoff D Vo, E Rowinsky
`
`Abstract:
`
`MTA (LY 231514) is a new antifol that inhibits multiple folate-dependent enzymes, including thymidylate synthase,
`dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. Initial phase I trials demonstrated major
`antitumor responses when MTA was given as a 10 min I.V. infusion, however, myelosuppression precluded dose
`escalation above 500-600 mg/m2. Since preclinical studies indicated that folic acid supplementation increases the
`eherapeutic index of MTA, the feasibility of administering folic acid 5 mg daily for 5 days starting 2 days before MTA
`in minimally- and heavily-pretreated pts was evaluated to determine if folic acid supplementation ameliorates the toxif
`effects of MTA, permitting significant dose-escalation above the recommended phase II dose of MTA alone. Thus far,
`21 pts with solid cancers have received 55 courses at the following dose levels: 600, 700, and 800 mg/m2. Drug-related
`toxicities have included neutropenia, anemia, and thrombocytopenia, which have been more severe in heavily-
`pretreated pts. Other toxicities (grade 1-2) include rash, somnolence, fatigue, leg edema, and diminished renal function
`manifested by a decrease in creatinine clearance. One pt taking a non-steroidal anti-inflammatory agent experienced
`severe toxicities at the 800 mg/m2 dose, which resolved after administration of leucovorin and thymidine. One partial
`response in a pt with metastatic colon cancer has been observed. PK and vitamin (folic acid) metabolite profiles were
`done during cycles 1 and 3 at 600 to 800 mg/m2. To date, serum folic acid levels do not appear to be related to toxicity,
`but homocysteine was significantly elevated in the pt with severe toxicities at the 800 mg/m2 dose. Thus far, heavily-
`and minimally-pretreated patients have tolerated MTA at 600 and 800 mg/m2 and accrual continues at 700 and 900
`
`ACCORD EX 1004
`
`
`
`ASCO University • Quality Oncology Practice Initiative (QOPI) • ASCO Connection
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`
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`Username:
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`will utilize to remember you by, thereby avoiding the need to enter username and password upon subsequent visits to ASCO.org. DO NOT select this option if you
`share this computer with others since transactional, personal, or member only information will be accessible by other users.
`
`To activate the Remember Me option, click the empty check box when signing in to the site. The Remember Me functionality is deactivated at the logout.
`
`For additional information please review our Privacy Policy.
`
`OK
`
`
`
`
`
` Donate
`
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`
`ASCO Home Meetings Abstracts 1998 ASCO Annual Meeting
`(cid:1) Practice &
` Home
` About ASCO
` MyASCO
` Cancer Portals
` Products
` Meetings
`Guidelines
`
`(cid:1) Research
`Resources
`(cid:1) Education &
`Training
`(cid:1) Public Policy
`(cid:1) International
`Affairs
`(cid:1) Grants &
`Awards
`(cid:1) MultiMedia
`(cid:1) Press Center
`
`A PHASE I AND PHARMACOKINETIC (PK) STUDY
`OF THE MULTITARGETED ANTIFOL (MTA)
`LY231514 WITH FOLIC ACID (Meeting abstract).
`
` Print this page
`
`
`
`Sub-category:
`Other
`
`Category:
`Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
`
`Meeting:
`1998 ASCO Annual Meeting
`
`Abstract No:
`866
`
`Author(s):
`L Hammond, M Villalona-Calero, SG Eckhardt, R Drengler, C Aylesworth, T Johnson, M Hidalgo, G Rodriguez, S
`Diab, P Monroe, D Thornton, Hoff D Vo, E Rowinsky
`
`Abstract:
`
`MTA (LY 231514) is a new antifol that inhibits multiple folate-dependent enzymes, including thymidylate synthase,
`dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. Initial phase I trials demonstrated major
`antitumor responses when MTA was given as a 10 min I.V. infusion, however, myelosuppression precluded dose
`escalation above 500-600 mg/m2. Since preclinical studies indicated that folic acid supplementation increases the
`eherapeutic index of MTA, the feasibility of administering folic acid 5 mg daily for 5 days starting 2 days before MTA
`in minimally- and heavily-pretreated pts was evaluated to determine if folic acid supplementation ameliorates the toxif
`effects of MTA, permitting significant dose-escalation above the recommended phase II dose of MTA alone. Thus far,
`21 pts with solid cancers have received 55 courses at the following dose levels: 600, 700, and 800 mg/m2. Drug-related
`toxicities have included neutropenia, anemia, and thrombocytopenia, which have been more severe in heavily-
`pretreated pts. Other toxicities (grade 1-2) include rash, somnolence, fatigue, leg edema, and diminished renal function
`manifested by a decrease in creatinine clearance. One pt taking a non-steroidal anti-inflammatory agent experienced
`severe toxicities at the 800 mg/m2 dose, which resolved after administration of leucovorin and thymidine. One partial
`response in a pt with metastatic colon cancer has been observed. PK and vitamin (folic acid) metabolite profiles were
`done during cycles 1 and 3 at 600 to 800 mg/m2. To date, serum folic acid levels do not appear to be related to toxicity,
`but homocysteine was significantly elevated in the pt with severe toxicities at the 800 mg/m2 dose. Thus far, heavily-
`and minimally-pretreated patients have tolerated MTA at 600 and 800 mg/m2 and accrual continues at 700 and 900
`
`ACCORD EX 1004
`
`
`
`mg/m2, respectively. These results indicate that folic acid supplementation appears to permit MTA dose escalation.
`
`
`
` Associated Presentation(s):
`
` No items found.
`
`
` Other Abstracts in this Sub-Category:
`
` 1. PHARMACOKINETICS OF IRINOTECAN AND ITS ACTIVE METABOLITE SN-38 IN CHILDREN
`WITH RECURRENT SOLID TUMORS AFTER PROTRACTED LOW DOSE IV IRINOTECAN (Meeting
`abstract).
`
`Meeting: 1998 ASCO Annual Meeting Abstract No: 715 First Author: Stewart C
`Category: Developmental Therapeutics - Clinical Pharmacology and Immunotherapy - Other
` 2. POPULATION PHARMACOKINETIC (PK) MODEL FOR TOPOTECAN (TPT) (Meeting abstract).
`
`Meeting: 1998 ASCO Annual Meeting Abstract No: 716 First Author: PB Laub
`Category: Developmental Therapeutics - Clinical Pharmacology and Immunotherapy - Other
` 3. CYCLOSPORIN A (CsA) STRONGLY ENHANCES ORAL BIOAVAILABILITY OF PACLITAXEL (pac)
`IN CANCER PATIENTS (Meeting abstract).
`
`Meeting: 1998 ASCO Annual Meeting Abstract No: 717 First Author: JH Schellens
`Category: Developmental Therapeutics - Clinical Pharmacology and Immunotherapy - Other
` More...
`
`
` Abstracts by L Hammond:
`
` 1. ILX651 administered daily for five days every 3 weeks (qdx5dq3w) in patients (pts) with inoperable locally
`advanced or metastatic melanoma:phase II experience
`
`Meeting: 2005 ASCO Annual Meeting Abstract No: 7556 First Author: D. F. McDermott
`Category: Melanoma/Skin Cancers - Melanoma
` 2. A phase I pharmacokinetic (PK) trial of XAA296A (Discodermolide) administered every 3 wks to adult
`patients with advanced solid malignancies.
`
`Meeting: 2004 ASCO Annual Meeting Abstract No: 2025 First Author: A. Mita
`Category: Developmental Therapeutics - Clinical Pharmacology and Immunotherapy -
`Pharmacology/Pharmacokinetics
` 3. A pharmacologic and metabolic study of docetaxel (D) administered on a continuous weekly schedule in
`patients with advanced solid tumors.
`
`Meeting: 2003 ASCO Annual Meeting Abstract No: 651 First Author: J. D. Rizzo
`Category: Developmental Therapeutics - Clinical Pharmacology and Immunotherapy -
`Pharmacology/Pharmacokinetics
` More...
`
`
` Presentations by L Hammond:
`
` 1. Phase (Ph) I evaluation of the dolastatin analogue synthadotin (SYN-D; ILX651): Pooled data analysis of three
`alternate schedules in patients (pts) with advanced solid tumors.
`
`Meeting: 2004 ASCO Annual Meeting
`Presenter: Lisa A. Hammond, MD
`Session: Developmental Therapeutics: Molecular Therapeutics (General Poster Session)
` 2. Phase 1 study of pemetrexed (LY231514) with vitamin supplementation in patients with locally advanced or
`metastatic cancer
`
`Meeting: 2003 ASCO Annual Meeting
`Presenter: Lisa A Hammond, MD
`Session: Developmental Therapeutics - Cytotoxic Chemotherapy (General Poster Session)
` 3. Phase I and pharmacokinetic (PK) trial of sequences of the rebeccamycin analog, NSC 655649, and cisplatin
`(CDDP)
`
`Meeting: 2002 ASCO Annual Meeting
`Presenter: Lisa A. Hammond, MD
`Session: Pharmacology (General Poster Session)
` More...
`
`
` Educational Book Manuscripts by L Hammond:
`
` No items found.
`
`
`
`
`
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