Purified compositions of 10-propargyl-10-deazaaminopterin and methods of using same in the treatment of tumors

• US 6,028,071 A
• Filed: 03/08/1999
• Issued: 02/22/2000
• Est. Priority Date: 07/17/1996
• Status: Expired due to Term

• Current Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center), Southwest Research Institute, SRI International, Inc.
• Original Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center), Southwest Research Institute, SRI International, Inc.
• Inventors: Sirotnak, Francis M., Piper, James R., DeGraw, Joseph I., Colwell, William T.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Sripada, Pavanaram K.
• Application Number:
  US09/214,984
• Time in Patent Office: 351 Days
• Field of Search: 544/259, 544/260, 514/249, 514/258
• US Class Current: 514/249
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 475/08 with a nitrogen atom directly attached in position 2

Abstract

Highly purified 10-propargyl-10-deazaaminopterin (10-propargyl-10dAM) compositions tested in xenograft models for their efficacy against human tumors are shown to be far superior to methotrexate ("MTX") and are even superior to the newer clinical candidate edatrexate ("EDX"). Moreover, 10-propragyl-10dAM showed a surprising ability to cure tumors such that there was no evidence of tumor growth several weeks after the cessation of therapy. Thus, highly purified compositions containing 10-propargyl-10dAM can be used to treat human tumors, particularly human mammary tumors and human lung cancer.

Claims

1. 10-Propargyl-10-deazaaminopterin, substantially free of 10-deazaaminopterin.

2. A composition consisting essentially of 10-Propargyl-10-deazaaminopterin.

3. A pharmaceutical composition comprising 10-Propargyl-10-deazaaminopterin, substantially free of 10-deazaaminopterin, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 3, further comprising at least one additional cytotoxic or antitumor compound.

10. The pharmaceutical composition according to claim 9, wherein the at least one additional cytotoxic or antitumor compound is selected from the group consisting of vinca alkaloids, 5-fluorouracil, alkylating agents, cisplatin, carboplatin, leucovorin, taxols and antibiotics.

4. A method for treatment of tumors comprising administering to a human patient diagnosed as having a tumor a therapeutically effective amount of 10-propargyl-10-deazaaminopterin, substantially free of 10-deazaaminopterin.

5. The method according to claim 4, wherein the tumor is a solid tumor.

6. The method according to claim 4, wherein the 10-propargyl-10-deazaaminopterin, substantially free of 10-deazaaminopterin, is administered in amounts of from 40 to 120 mg/m² of body surface area/day.

7. The method according to claim 5, wherein the tumor is a mammary tumor.

8. The method according to claim 4, wherein the tumor is a lung tumor.

11. The method according to claim 4, wherein at least one additional cytotoxic or antitumor compound is administered with the therapeutically effective amount of 10-propargyl-1-deazaaminopterin, substantially free of 10-deazaaminopterin.

12. The method according to claim 11, wherein the at least one additional cytotoxic or antitumor compound is selected from the group consisting of vinca alkaloids, 5-fluorouracil, alkylating agents, cisplatin, carboplatin, leucovorin, taxols and antibiotics.