Novel antifolate drugs

Current Oncology Reports

Volumn 5, Issue 2, 2003, Pages 114-125

  Purcell, W Thomas ^a   Ettinger, David S ^b  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

2 [5 [[(1,2 DIHYDRO 3 METHYL 1 OXOBENZO[F]QUINAZOLIN 9 YL)METHYL]AMINO] 1 OXO 2 ISOINDOLINYL]GLUTARIC ACID; CAPECITABINE; CISPLATIN; COBALAMIN; CYTARABINE; DIHYDROFOLATE REDUCTASE; DOCETAXEL; DOXORUBICIN; EDATREXATE; FLUOROURACIL; FOLIC ACID; FOLIC ACID ANTAGONIST; FOLINIC ACID; GEMCITABINE; GW 1843; IRINOTECAN; LOMETREXOL; MERCAPTOPURINE; METHOTREXATE; N [5 [2 (2 AMINO 1,4,5,6,7,8 HEXAHYDRO 4 OXOPYRIDO[2,3 D]PYRIMIDIN 6 YL)ETHYL] 2 THENOYL]GLUTAMIC ACID; NOLATREXED; OXALIPLATIN; PEMETREXED; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; PLEVITREXED; RALTITREXED; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; THYMIDYLATE SYNTHASE; TRIMETREXATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE; ANTINEOPLASTIC ANTIMETABOLITE;

ANEMIA; APOPTOSIS; ASTHENIA; BONE MARROW SUPPRESSION; BREAST CANCER; CLINICAL TRIAL; COLORECTAL CANCER; DEHYDRATION; DIARRHEA; DRUG ERUPTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TARGETING; DRUG TRANSPORT; ENZYME INHIBITION; FEVER; GENE AMPLIFICATION; HEMATOLOGIC MALIGNANCY; HUMAN; LEUKOPENIA; LIVER DYSFUNCTION; LUNG CANCER; MESOTHELIOMA; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; PNEUMOCYSTIS PNEUMONIA; PROTEIN TARGETING; REVIEW; SOLID TUMOR; THROMBOCYTOPENIA; VOMITING; CHEMISTRY; DRUG RESISTANCE;

ANTIMETABOLITES, ANTINEOPLASTIC; CLINICAL TRIALS; DRUG RESISTANCE, NEOPLASM; FOLIC ACID ANTAGONISTS; HUMANS;

EID: 0642316402     PISSN: 15233790     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11912-003-0098-3     Document Type: Review

References (113)

1. Fleming GF, Schilsky RL: Antifolates: the next generation. Semin Oncol 1992, 19:707-719.
2. Takimoto CH, Allegra CJ: New antifolates in clinical development. Oncology (Huntingt) 1995, 9:649-656, 659.
3. Takimoto CH: New antifolates: pharmacology and clinical applications. Oncologist 1996, 1:68-81.
4. Takimoto CH: Antifolates in clinical development. Semin Oncol 1997, 24:S18.
5. Adjei AA: A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. Br J Clin Pharmacol 1999, 48:265-277.
6. Curtin NJ, Hughes AN: Pemetrexed disodium: a novel antifolate with multiple targets. Lancet Oncol 2001, 2:298-306.
7. Fizazi K, John WJ, Vogelzang NJ: The emerging role of antifolates in the treatment of malignant pleural mesothelioma. Semin Oncol 2002, 29:77-81.
8. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol 2002, 29:50-53.
9. Matherly LH: Molecular and cellular biology of the human reduced folate carrier. Prog Nucleic Acid Res Mol Biol 2001, 67:131-162.
10. Messmann RA, Allegra CJ: Antifolates. In Cancer Chemotherapy and Biotherapy, edn 3. Edited by Chabner B, Longo D. Philadelphia: Lippincott, Williams & Wilkins; 2001.
11. Wang Y, Zhao R, Chattopadhyay S, Goldman ID: A novel folate transport activity in human mesothelioma cell lines with high affinity and specificity for the new-generation antifolate, pemetrexed. Cancer Res 2002, 62:6434-6437.
12. Chu E, Mota AC, Fogarasi MC: Antimetabolites. In Cancer: Principles and Practice of Oncology, edn 6. Edited by De Vita VT, Hellman S, Rosenberg SA. Philadelphia: Lippincott, Williams & Wilkins; 2001:388-415.
13. Sun X, Cross JA, Bognar AL, et al.: Folate-binding triggers the activation of folylpolyglutamate synthetase. J Mol Biol 2001, 310:1067-1078.
14. Longo-Sorbello GS, Bertino JR: Current understanding of methotrexate pharmacology and efficacy in acute leukemias: use of newer antifolates in clinical trials. Haematologica 2001, 86:121-127.
15. Kisliuk RL: Synergistic interactions among antifolates. Pharmacol Ther 2000, 85:183-190.
16. Caperelli CA, Giroux EL: The human glycinamide ribonucleotide transformylase domain: purification, characterization, and kinetic mechanism. Arch Biochem Biophys 1997, 341:98-103.
17. Vergis JM, Bulock KG, Fleming KG, Beardsley GP: Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/Inosine 5′-monophosphate cyclohydrolase: a bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity. J Biol Chem 2001, 276:7727-7733.
18. Papamichael D: The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status. Oncologist 1999, 4:478-487.
19. Matherly LH, Taub JW: Methotrexate pharmacology and resistance in childhood acute lymphoblastic leukemia. Leuk Lymphoma 1996, 21:359-368.
20. Gorlick R, Cole P, Banerjee D, et al.: Mechanisms of methotrexate resistance in acute leukemia: decreased transport and polyglutamylation. Adv Exp Med Biol 1999, 457:543-550.
21. Banerjee D, Mayer-Kuckuk P, Capiaux G, et al.: Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochimi Biophys Acta 2002, 1587:164-173.
22. Takemura Y, Kobayashi H, Miyachi H: Antifolate resistance and its circumvention by new analogues. Hum Cell 2001, 14:185-202.
23. Ouellette M, Leblanc E, Kundig C, Papadopoulou B: Antifolate resistance mechanisms from bacteria to cancer cells with emphasis on parasites. Adv Exp Med Biol 1998, 456:99-113.
24. Gorlick R, Cole P, Banerjee D, et al.: Mechanisms of methotrexate resistance in acute leukemia: decreased transport and polyglutamylation. Adv Exp Med Biol 1999, 457:543-550.
25. Moscow JA: Methotrexate transport and resistance. Leuk Lymphoma 1998, 30:215-224.
26. Kinsella AR, Smith D: Tumor resistance to antimetabolites. Gen Pharmacol 1998, 30:623-626.
27. Guo W, Healey JH, Meyers PA, et al.: Mechanisms of methotrexate resistance in osteosarcoma. Clin Cancer Res 1999, 5:621-627.
28. Ulrich CM, Robien K, Sparks R: Pharmacogenetics and folate metabolism: a promising direction. Pharmacogenomics 2002, 3:299-313.
29. Guo B, Cao S, Toth K, Azrak RG, Rustum YM: Overexpression of Bax enhances antitumor activity of chemotherapeutic agents in human head and neck squamous cell carcinoma. Clin Cancer Res 2000, 6:718-724.
30. Kamen B: Folate and antifolate pharmacology. Semin Oncol 1997, 24:S18.
31. Heusner JJ, McCormack JJ: Enzymatic assays for 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline, a promising new 'nonclassical' antifolate. J Pharmacol Sci 1981, 70:827-828.
32. Punt CJ, Blanke CD, Zhang I, Hammershaimb L: Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer. Ann Oncol 2002, 13:92-94.
33. Blanke CD, Shultz J, Cox J, et al.: A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer. Ann Oncol 2002, 13:87-91.
34. Punt CJA, Blanke CD, Zhang J, Hammershaimb L: Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer. Ann Oncol 2002, 13:92-94.
35. Ramanathan RK, Jacobs SA: Phase I/II study of trimetrexat (TMTX) and capecitabine (CAP) as second and third line therapy in patients with advanced colorectal tumors (CRC). [abstract]. Proc ASCO 2002, 21:2255.
36. Kris MG, Kinahan JJ, Gralla RJ, et al.: Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer. Cancer Res 1988, 48:5573-5579.
37. Nair MG, Nanavati NT, Kumar P, et al.: Synthesis and biological evaluation of poly-gamma-glutamyl metabolites of 10-deazaaminopterin and 10-ethyl-10-deazaaminopterin. J Med Chem 1988, 31:181-185.
38. Grant SC, Kris MG, Young CW, Sirotnak FM: Edatrexate, an antifolate with antitumor activity: a review. Cancer Invest 1993, 11:36-45.
39. Colon-Otero G, Marschke R, Camoriano JK, et al.: A dose-seeking trial of edatrexate in combination with vinblastine, adriamycin, cisplatin, and filgrastim (EVAC/G-CSF) in patients with advanced malignancies: promising antineoplastic activity against non-small cell lung carcinomas. Cancer J Sci Am 1997, 3:297-302.
40. Colon-Otero G, Niedringhaus RD, Hillman SH, et al.: A phase II trial of edatrexate, vinblastine, adriamycin, cisplastin, and filgrastim (EVAC/G-CSF) in patients with non-small-cell carcinoma of the lungs: a North Central Cancer Treatment Group Trial. Am J Clin Oncol 2001, 24:551-555.
41. Van Cutsem E, Cunningham D, Maroun J, et al.: Raltitrexed: current clinical status and future directions. Ann Oncol 2002, 13:513-522.
42. Cocconi G, Cunningham D, Van Cutsem E, et al.: Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. J Clin Oncol 1998, 16:2943-2952.
43. Cunningham D, Zalcberg J, Maroun J, et al.: Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer: a review of phase II/III trials. Eur J Cancer 2002, 38:478-486.
44. Neri B, Doni L, Fulignati C, et al.: Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal carcinoma: a multicentric phase II trial. Anticancer Drugs 2002, 13:719-724.
45. Lewis NL, Scher R, Gallo JM, et al.: Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed. Cancer Chemother Pharmacol 2002, 50:257-265.
46. Caponigro F, Rosati G, De Rosa P, et al.: Cisplatin, raltitrexed, levofolinic acid and 5-fluorouracil in locally advanced or metastatic squamous cell carcinoma of the head and neck: a phase II randomized study. Oncology 2002, 63:232-238.
47. Comella P, Casaretti R, Crucitta E, et al.: Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients. Br J Cancer 2002, 86:1871-1875.
48. Costa F: Irinotecan (CPT-11), oxaliplatin (OHP), and raltitrexed every two weeks in untreated metastatic colorectal cancer (CRC) patients [abstract]. Proc ASCO, 2002, 21:2438a.
49. Maroun J: Phase I study of triple drug combination of CPT-11 (C), oxaliplatin (O) and tomudex (T) (COT) in previously untreated patients (pts) with metastatic colorectal cancer (MCRC): National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), IND.135 [abstract]. Proc ASCO 2002, 21:571a.
50. Aparicio J, Vicent JM: Ongoing phase II trial with a three-weekly schedule of irinotecan (CPT-11) and raltitrexed (ZD) for first-line treatment in advanced colorectal cancer (ACC) [abstract]. Proc ASCO 2002, 21:2220a.
51. Martoni A, Mini E: Phase II study of oxaliplatin (OHP) and raltitrexed (RTX) in chemonaive and pretreated advanced colorectal cancer (ACRC) patients [abstract]. Proc ASCO, 2002, 21:689a.
52. Girón GC, Salut A: Phase II trial of irinotecan (IRI) and raltitrexed (RTD) administered every two weeks in chemotherapy naive advanced colorectal cancer (ACRC) patients [abstract]. Proc ASCO 2002, 21:685a.
53. Valentini V: Raltitrexed ('Tomudex') and oxaliplatin (Tomox) preliminary results of a phase II study of chemoradiation with pre-operative treatment of stage II/III resectable rectal cancer [abstract]. Proc ASCO 2002, 21:603a.
54. Avallone P, Delrio C: Oxaliplatin (OXA) + raltitrexed (TOM) + FUFA and preoperative concomitant radiotherapy (RT) for locally advanced rectal cancer (LARC): a phase I study [abstract]. Proc ASCO 2002, 21:2128a.
55. Raats J, Rapoport B: A phase I/II clinical trial of cisplatin and raltitrexed (Tomudex) in newly diagnosed patients with metastatic carcinoma of unknown primary (CUP) [abstract]. Proc ASCO 2002, 21:2193a.
56. Slabber CF, Vorobiof DA: Significant responses with cisplatin based therapy in patients with metastatic breast cancer refractory to anthracycline or anthracycline and taxanes: results of a phase I/II trial of cisplatin and raltitrexed [abstract]. Proc ASCO 2002, 21:1999a.
57. Jones RJ, Twelves CJ: Pemetrexed: a multitargeted antifolate (ALIMTA, LY-231514). Expert Rev Anticancer Ther 2002, 2:13-22.
58. Hanauske AR: Pemetrexed: translational research in breast cancer. Semin Oncol 2002, 29:40-42.
59. Calvert H, Bunn PA, Jr: Future directions in the development of pemetrexed. Semin Oncol 2002, 29:54-61.
60. Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs 2001, 2:1611-1622.
61. Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist 2001, 6:363-373.
62. Adjei AA: Pemetrexed: a multitargeted antifolate agent with promising activity in solid tumors. Ann Oncol 2000, 11:1335-1341.
63. Calvert H: MTA, a novel multitargeted antifolate, from preclinical to phase I and beyond: summary and conclusions. Semin Oncol 1999, 26:105-108.
64. Schultz RM, Chen VJ, Bewley JR, et al.: Biological activity of the multitargeted antifolate, MTA (LY231514), in human cell lines with different resistance mechanisms to antifolate drugs. Semin Oncol 1999, 26:68-73.
65. Schultz RM, Patel VF, Worzalla JF, Shih C: Role of thymidylate synthase in the antitumor activity of the multitargeted antifolate, LY231514. Anticancer Res 1999, 19:437-443.
66. Calvert H: Folate status and the safety profile of antifolates. Semin Oncol 2002, 29:3-7.
67. Worzalla JF, Shih C, Schultz RM: Role of folic acid in modulating the toxicity and efficacy of the multitargeted antifolate, LY231514. Anticancer Res 1998, 18:3235-3239.
68. Shin DM: A phase II trial of pemetrexed in malignant pleural mesothelioma (MPM) patients: clinical outcome, role of vitamin supplementation, respiratory symptoms and lung function. [abstract]. Proc ASCO 2002, 21:1175a.
69. Rinaldi DA, Kuhn JG, Burris HA, et al.: A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation. Cancer Chemother Pharmacol 1999, 44:372-380.
70. Fossella FV, Gatzemeier U: Phase I trials of pemetrexed. Semin Oncol 2002, 29:8-16.
71. Green MR: Alimta (pemetrexed disodium): a multitargeted antifolate for the treatment of mesothelioma. Lung Cancer 2002, 38:55-57.
72. Vogelzang NJ: Phase III single-blinded study of pemetrexed + cisplatin vs. cisplatin alone in chemonaive patients with malignant pleural mesothelioma [abstract]. Proc ASCO 2002, 21:5a.
73. Rusthoven JJ, Eisenhauer E, Butts C, et al.: Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non-small-cell lung cancer: a phase II study. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1999, 17:1194.
74. Clarke SJ, Abratt R, Goedhals L, et al.: Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naive patients with advanced non-small-cell lung cancer. Ann Oncol 2002, 13:737-741.
75. Postmus PE: Activity of pemetrexed (alimta), a new antifolate, against non-small cell lung cancer. Lung Cancer 2002, 38:3-7.
76. Manegold C, Gatzemeier U, von Pawel J, et al.: Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial. Ann Oncol 2000, 11:435-440.
77. Shepherd FA, Dancey J, Arnold A, et al.: Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin as first-line therapy in patients with advanced nonsmall cell lung carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. Cancer 2001, 92:595-600.
78. Rosell R, Crino L: Pemetrexed combination therapy in the treatment of non-small cell lung cancer. Semin Oncol 2002, 29:23-29.
79. Ettinger DS: Gemcitabine/Alimta in locally advanced or metastatic non-small-cell lung cancer. Oncology (Huntingt) 2000, 14:49-52.
80. Ettinger DS, Bunn PA, Le Chevalier T, et al.: Gemcitabine + ALIMTA(TM) in advanced non-small cell lung cancer (NSCLC): Why this regimen? Lung Cancer 2000, 29:58-59.
81. Le Chevalier T: Gemcitabine and pemetrexed (Alimta) in thoracic cancers: present and future perspectives: introduction and current controversies. Semin Oncol 2002, 29:43-46.
82. Novello S, Le Chevalier T: ALIMTA (pemetrexed disodium, LY231514, MTA): clinical experience in non-small cell lung cancer. Lung Cancer 2001, 34(Suppl 4):S107-S109.
83. Ettinger DS, Monnerat C: Phase II trial of pemetrexed + gemcitabine in patients with advanced non-small cell lung cancer: importance of survival over response [abstract]. Proc ASCO 2002, 21:1243a.
84. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer 2001, 34(Suppl 4): S103-S105.
85. Adjei AA: Comparing three schedules of Alimta plus Gemzar: a phase II randomized study. http://www.clinicaltrials.gov/
86. O'Shaughnessy JA, Gennari A, Conte P: Pemetrexed: a promising new treatment for breast cancer. Semin Oncol 2002, 29:36-41.
87. Adjei AA: Pemetrexed (Alimta) and gemcitabine in breast cancer patients previously treated with anthracyclines and taxanes. Clin Breast Cancer 2002, 3(Suppl 1):21-23.
88. Adjei AA: Gemcitabine and pemetrexed disodium in treating breast cancer. Oncology (Huntingt) 2001, 15:34-37.
89. Kindler HL: The pemetrexed/gemcitabine combination in pancreatic cancer. Cancer 2002, 95:928-932.
90. De Gramont A, Kindler HL: Pemetrexed in patients with gastrointestinal carcinoma. Semin Oncol 2002, 29:42-49.
91. Pivot X, Raymond E, Laguerre B, et al.: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer 2001, 85:649-655.
92. Jackman AL, Melin CJ, Kimbell R, et al.: A rationale for the clinical development of the thymidylate synthase inhibitor ZD9331 in ovarian and other solid tumours. Biochim Biophys Acta 2002, 1587:215-223.
93. Niculescu-Duvaz I: ZD-9331 AstraZeneca. Curr Opin Investig Drugs 2000, 1:141-149.
94. Goh BC, Ratain MJ, Bertucci D, et al.: Phase I study of ZD9331 on short daily intravenous bolus infusion for 5 days every 3 weeks with fixed dosing recommendations. J Clin Oncol 2001, 19:1476-1484.
95. Britten CD: A phase I and pharmacokinetic (PK) study of ZD9331, a nonpolyglutaminated thymidylate synthase (TS) inhibitor, administered once every 3 weeks [abstract]. Proc ASCO 1998, 17:622a.
96. Rha Y: Determination of the variables affecting the clearance (CL) of the novel thymidylate synthase (TS) inhibitor, ZD9331 [abstract]. Proc ASCO 1999, 18:652a.
97. Rees C, Beale P, Trigo J, et al.: Phase I trial of ZD9331, a non-polyglutamatable thydimylate synthase (TS) inhibitor given as a five day continuous infusion every 3 weeks [abstract]. Proc ASCO 1999.
98. de Jonge MJ, Punt CJ, Sparreboom A, et al.: Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors. J Clin Oncol 2002, 20:1923-1931.
99. de Jonge MJ, Glimelius B, Verweij J, et al.: Effects of impaired renal function on the pharmacokinetics and toxicity of i.v. ZD9331, a novel non-polyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors. Anticancer Drugs 2002, 13:645-653.
100. Smith DB, Gallagher N: A phase II/III trial of efficacy and tolerability of ZD9331 vs gemcitabine in pancreatic cancer [abstract]. Proc ASCO 2002, 21:574a.
101. Petruzelka LB, Wojtukiewicz MZ: ZD9331, a novel antifolate, in the first-line treatment of gastric cancer [abstract]. Proc ASCO 2002, 21:595a.
102. Kahanic S, Hainsworth JD: ZD9331, a novel antifolate, as second-line therapy in non-small cell lung cancer: a phase II multicenter trial [abstract]. Proc ASCO 2002, 21:2682a.
103. Wood S, Schwartz G: A phase I, dose-escalating trial of ZD9331 in combination with docetaxel in patients with refractory solid malignancies [abstract]. Proc ASCO 2002, 21:1843a.
104. Louvet C, Andre T: A phase I/II intra-patient dose escalating trial of ZD9331 in combination with irinotecan (CPT11) as second-line treatment for patients (pts) with metastatic colorectal cancer [abstract]. Proc ASCO 2002, 21:2288a.
105. Takimoto CH: New antifolates: pharmacology and clinical applications. Oncologist 1996, 1:68-81.
106. Bronder JL, Moran RG: Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 function. Cancer Res 2002, 62:5236-5241.
107. Roberts JD, Poplin EA, Tombes MB, et al.: Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation. Cancer Chemother Pharmacol 2000, 45:103-110.
108. Sessa C, de Jong J, D'Incalci M, et al.: Phase I study of the antipurine antifolate lometrexol (DDATHF) with folinic acid rescue. Clin Cancer Res 1996, 2:1123-1127.
109. Budman DR, Johnson R, Barile B, et al.: Phase I and pharmacokinetic study of LY309887: a specific inhibitor of purine biosynthesis. Cancer Chemother Pharmacol 2001, 47:525-531.
110. Schwartz G, Johnson TR, Goetz A, et al.: A phase I and pharmacokinetic study of 1843U89, a noncompetitive inhibitor of thymidylate synthase, in patients with advanced solid malignancies. Clin Cancer Res 2001, 7:1901-1911.
111. OSI Pharmaceuticals. Press release at annual meeting of the American Association for Cancer Research. San Francisco, CA, April 6-10, 2002.
112. Pivot X, Wadler S, Kelly C, et al.: Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer. Ann Oncol 2001, 12:1595-1599.
113. Niculescu-Duvaz I: Thymitaq (Zarix). Curr Opin Investig Drugs 2001, 2:693-705.