US2004071774A1PendingUtilityA1

Methods for treating ovarian cancer, poly (phosphoester) compositions, and biodegradable articles for same

Priority: Jan 11, 1999Filed: Aug 14, 2003Published: Apr 15, 2004

Est. expiryJan 11, 2019(expired)· nominal 20-yr term from priority

Inventors:Wenbin Dang

A61K 9/1647A61P 35/00Y10S977/912Y10S977/911A61K 9/7007A61K 47/30

PatentIndex Score

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References

Claims

Abstract

Biodegradable polymer compositions suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer are described, wherein the polymer compositions provide extended release of the antineoplastic agent into the peritoneum of the subject. The subject compositions can increase the median survival rate from the cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of the antineoplastic agent without the biodegradable polymer. Solid articles and methods for treating ovarian cancer are also described.

Claims

exact text as granted — not AI-modified

I claim:

1 . A biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula I: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said polymer composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

2 . The composition of claim 1 wherein said polymer composition increases the median survival rate from said cancer by at least about 20%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

3 . The polymer composition of claim 1 wherein said composition increases the median survival rate from said cancer by at least about 30%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

4 . The polymer composition of claim 1 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

5 . The polymer composition of claim 1 wherein said polymer is selected from the group consisting of:

wherein:
M 1 and M 2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms;
the molar ratio of x:y is about 1;
the molar ratio n:(x or y) is between about 200:1 and 1:200; and
the molar ratio q:r is between about 1:99 and 99:1.

6 . A biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula IV: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; M 1 and M 2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atom; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; the molar ratio q:r is between about 1:99 and 99:1; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

7 . The polymer composition of claim 6 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

8 . The composition of claim 6 wherein each of M 1 , M 2 and L is a branched or straight chain alkylene group.

9 . The composition of claim 6 wherein each of M 1 , M 2 and L has from 1 to 7 carbon atoms.

10 . The composition of claim 6 wherein each of M 1 and M 2 is an ethylene group or a methyl-substituted methylene group, and L is an ethylene group.

11 . The composition of claim 6 wherein R 3 is an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, or a heterocycloxy group.

12 . The composition of claim 6 wherein R 3 is an alkoxy group having from 1 to 7 carbon atoms.

13 . The composition of claim 6 wherein R 3 is an ethoxy group.

14 . The composition of claim 6 wherein each of M 1 and M 2 is a branched or straight chain alkylene group.

15 . The composition of claim 6 wherein at least one of M 1 and M 2 is an alkylene or alkoxylene group having a formula selected from the group consisting of —(CH 2 ) a —, —(CH 2 ) a —O—, and —(CH 2 ) a —O—(CH 2 ) b —, wherein each of a and b is an integer from 1 to 7.

16 . The composition of claim 6 wherein at least one of M 1 and M 2 has the formula: —CHR′—CO—O—CHR″—, wherein R′ and R″ are each independently H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy.

17 . The composition of claim 6 wherein each of M 1 and M 2 has from 1 to 7 carbon atoms.

18 . The composition of claim 6 wherein X is —O—.

19 . The composition of claim 6 wherein X is —NR 4 —.

20 . The composition of claim 6 wherein:
M 1 and M 2 are each an alkylene or alkoxylene group;
L is an alkylene group;
X is —O—; and
R 3 is an alkoxy group.

21 . The composition of claim 6 wherein the molar ratio x:y is about 1.

22 . The composition of claim 6 wherein the molar ratio q:r is about 1:99 and 99:1.

23 . The composition of claim 6 wherein each of x and y is about 1 to 1,000.

24 . The composition of claim 6 wherein the molar ratio n:(x or y) is between about 100:1 and 1:100.

25 . A biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula V: wherein each of R 1 and R 2 is independently straight or branched aliphatic, either unsubstituted or substituted with one or more non-interfering substituents; L is a divalent cycloaliphatic group; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

26 . The polymer composition of claim 25 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

27 . The composition of claim 25 wherein each of R 1 and R 2 is a branched or straight chain alkylene group having from one to seven carbon atoms.

28 . The composition of claim 25 wherein each of R 1 and R 2 is a methylene group or an ethylene group.

29 . The composition of claim 25 wherein R 3 is an alkoxy group.

30 . The composition of claim 25 wherein R 3 is hexyloxy.

31 . The composition of claim 25 wherein n is 5 to 500.

32 . The composition of claim 25 wherein L is a cycloaliphatic group, either unsubstituted or substituted with a non-interfering substituent.

33 . The composition of claim 25 wherein L is cyclohexylene.

34 . The composition of claim 1 wherein said polymer is prepared by solution polymerization.

35 . The composition of claim 1 wherein said polymer is prepared by melt polymerization.

36 . The composition of claim 1 wherein said polymer comprises additional biocompatible monomeric units or is blended with other biocompatible polymers.

37 . The composition of claim 1 wherein said polymer is soluble in at least one of the solvents selected from the group consisting of acetone, dimethylene chloride, chloroform, ethyl acetate, DMAC, N-methylpyrrolidone, dimethylformamide and dimethylsulfoxide.

38 . The composition of claim 1 wherein said antineoplastic agent comprises paclitaxel.

39 . The composition of claim 1 wherein the molecular weight (Mw) of said polymer is from about 2,000 to 400,000 daltons.

40 . The composition of claim 1 wherein said antineoplastic agent and said polymer form an amorphous, monolithic matrix.

41 . The composition of claim 1 in the form of microparticles, a flexible film, a viscous liquid, wafers or rods.

42 . The composition of claim 1 in the form of spray-dried microspheres.

43 . The composition of claim 1 wherein the composition comprises about 5-15% by weight of the antineoplastic agent.

44 . A biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) paclitaxel and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula VI: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said polymer composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

45 . A solid article suitable for insertion into the peritoneum to treat a mammalian subject having ovarian cancer, said article comprising a biodegradable polymer composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula I: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

46 . The article of claim 45 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

47 . The article of claim 45 wherein said composition increases the median survival rate from said cancer by at least about 20%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

48 . The article of claim 45 wherein said composition increases the median survival rate from said cancer by at least about 30%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

49 . The article of claim 45 wherein said polymer is selected from the group consisting of:

50 . A solid article suitable for insertion into the peritoneum to treat a mammalian subject having ovarian cancer, said article comprising a biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula IV: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; M 1 and M 2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; the molar ratio q:r is between about 1:99 and 99:1; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

51 . The article of claim 50 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

52 . The article of claim 50 wherein each of M 1 , M 2 and L is a branched or straight chain alkylene group.

53 . The article of claim 50 wherein each of M 1 , M 2 and L has from 1 to 7 carbon atoms.

54 . The article of claim 50 wherein each of M 1 and M 2 is an ethylene group or a methyl-substituted methylene group, and L is an ethylene group.

55 . The article of claim 50 wherein R 3 is an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, or a heterocycloxy group.

56 . The article of claim 50 wherein R 3 is an alkoxy group having from 1 to 7 carbon atoms.

57 . The article of claim 50 wherein R 3 is an ethoxy group.

58 . The article of claim 50 wherein each of M 1 and M 2 is a branched or straight chain alkylene group.

59 . The article of claim 50 wherein at least one of M 1 and M 2 is an alkylene or alkoxylene group having a formula selected from the group consisting of —(CH2) a —, —(CH2) a —O—, and —(CH2) a —O—(CH2) b —, wherein each of a and b is an integer from 1 to 7.

60 . The article of claim 50 wherein at least one of M 1 and M 2 has the formula: —CHR′—CO—O—CHR″—, wherein R′ and R″ are each independently H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy.

61 . The article of claim 50 wherein each of M 1 and M 2 has from 1 to 7 carbon atoms.

62 . The article of claim 50 wherein X is —O—.

63 . The article of claim 50 wherein X is —NR 4 —.

64 . The article of claim 50 wherein:
M 1 and M 2 are each an alkylene or alkoxylene group;
L is an alkylene group;
X is —O—; and
R 3 is an alkoxy group.

65 . The article of claim 50 wherein the molar ratio x:y is about 1.

66 . The article of claim 50 wherein the molar ratio q:r is about 1:99 and 99:1.

67 . The article of claim 50 wherein each of x and y is about 1 to 1,000.

68 . The article of claim 50 wherein the molar ratio n:(x or y) is between about 100:1 and 1:100.

69 . A solid article suitable for insertion into the peritoneum to treat a mammalian subject having ovarian cancer, said article comprising a biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula V: wherein each of R 1 and R 2 is independently straight or branched aliphatic, either unsubstituted or substituted with one or more non-interfering substituents; L is a divalent cycloaliphatic group; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the-median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

70 . The article of claim 69 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

71 . The article of claim 69 wherein each of R 1 and R 2 is a branched or straight chain alkylene group having from one to seven carbon atoms.

72 . The article of claim 69 wherein each of R 1 and R 2 is a methylene group or an ethylene group.

73 . The article of claim 69 wherein R 3 is an alkoxy group.

74 . The article of claim 69 wherein R 3 is hexyloxy.

75 . The article of claim 69 wherein n is 5 to 500.

76 . The article of claim 69 wherein L is a cycloaliphatic group, either unsubstituted or substituted with a non-interfering substituent.

77 . The article of claim 69 wherein L is cyclohexylene.

78 . The article of claim 69 wherein said polymer is prepared by solution polymerization.

79 . The article of claim 45 wherein said polymer is prepared by melt polymerization.

80 . The article of claim 45 wherein said polymer comprises additional biocompatible monomeric units or is blended with other biocompatible polymers.

81 . The article of claim 45 wherein said polymer is soluble in at least one of the solvents selected from the group consisting of acetone, dimethylene chloride, chloroform, ethyl acetate, DMAC, N-methylpyrrolidone, dimethylformamide and dimethylsulfoxide.

82 . The article of claim 45 wherein said antineoplastic agent comprises paclitaxel.

83 . The article of claim 45 wherein the molecular weight (Mw) of said polymer is from about 2,000 to 400,000 daltons.

84 . The article of claim 45 wherein said antineoplastic agent and said polymer form an amorphous, monolithic matrix.

85 . The article of claim 45 wherein said antineoplastic agent is encapsulated within said polymer.

86 . The article of claim 45 wherein said article results in minimal irritation to non-neoplastic tissues when implanted or injected into vasculated tissue.

87 . The article of claim 45 wherein said article is in the form of a flexible film, a wafer or a rod.

88 . The article of claim 45 wherein said article is in the form of one or more injectable microparticles.

89 . The article of claim 45 in the form of spray-dried microspheres.

90 . The article of claim 45 wherein the composition comprises about 5-15% by weight of the antineoplastic agent.

91 . A solid article suitable for insertion into the peritoneum to treat a mammalian subject having ovarian cancer, said article comprising a biodegradable polymer composition suitable for intraperitoneal administration to treat a mammalian subject having ovarian cancer, said composition comprising:
(a) paclitaxel and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula VI: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein said polymer composition provides extended release of said antineoplastic agent into the peritoneum of said subject; and wherein said composition increases the median survival rate of said mammalian subject from said cancer by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

92 . A method for treating a mammalian subject having ovarian cancer, by the extended release of an antineoplastic agent, said method comprising the steps of:
(a) combining the antineoplastic agent with a biodegradable polymer having the recurring monomeric units shown in formula I: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is 5-5,000; to form a composition; and (b) inserting said composition in vivo into the peritoneum of said subject, such that the inserted composition is in at least partial contact with an ovarian cancer tumor, wherein the median survival rate of said mammalian subject from said cancer is increased by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

93 . The method of claim 92 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

94 . The method of claim 92 wherein said composition increases the median survival rate from said cancer by at least about 20%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

95 . The method of claim 92 wherein said composition increases the median survival rate from said cancer by at least about 30%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

96 . The method of claim 92 wherein said polymer is selected from the group consisting of:

97 . A method for treating a mammalian subject having ovarian cancer, by the extended release of an antineoplastic agent, said method comprising the steps of:
(a) combining the antineoplastic agent with a biodegradable polymer having the recurring monomeric units shown in formula IV: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; M 1 and M 2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atom; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; the molar ratio q:r is between about 1:99 and 99:1; and n is about 5-5,000; and (b) inserting said composition in vivo into the peritoneum of said subject, such that the inserted composition is in at least partial contact with an ovarian cancer tumor, wherein the median survival rate of said mammalian subject from said cancer is increased by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

98 . The method of claim 97 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

99 . The method of claim 97 wherein each of M 1 , M 2 and L is a branched or straight chain alkylene group.

100 . The method of claim 97 wherein each of M 1 , M 2 and L has from 1 to 7 carbon atoms.

101 . The method of claim 97 wherein each of M 1 and M 2 is an ethylene group or a methyl-substituted methylene group, and L is an ethylene group.

102 . The method of claim 97 wherein R 3 is an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, or a heterocycloxy group.

103 . The method of claim 97 wherein R 3 is an alkoxy group having from 1 to 7 carbon atoms.

104 . The method of claim 97 wherein R 3 is an ethoxy group.

105 . The method of claim 97 wherein each of M 1 and M 2 is a branched or straight chain alkylene group.

106 . The method of claim 97 wherein at least one of M 1 and M 2 is an alkylene or alkoxylene group having a formula selected from the group consisting of —(CH2) a —, —(CH2) a —O—, and —(CH2) a —O—(CH2) b —, wherein each of a and b is an integer from 1 to 7.

107 . The method of claim 97 wherein at least one of M 1 and M 2 has the formula: —CHR′—CO—O—CHR″—, wherein R′ and R″ are each independently H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy.

108 . The method of claim 97 wherein each of M 1 and M 2 has from 1 to 7 carbon atoms.

109 . The method of claim 97 wherein X is —O—.

110 . The method of claim 97 wherein X is —NR 4 —.

111 . The method of claim 97 wherein:
M 1 and M 2 are each an alkylene or alkoxylene group;
L is an alkylene group;
X is —O—; and
R 3 is an alkoxy group.

112 . The method of claim 97 wherein the molar ratio x:y is about 1.

113 . The method of claim 97 wherein the molar ratio q:r is about 1:99 and 99:1.

114 . The method of claim 97 wherein each of x and y is about 1 to 1,000.

115 . The method of claim 97 wherein the molar ratio n:(x or y) is between about 100:1 and 1:100.

116 . A method for treating a mammalian subject having ovarian cancer, by the extended release of an antineoplastic agent, said method comprising the steps of:
(a) combining the antineoplastic agent with a biodegradable polymer having the monomeric units shown in formula V: wherein each of R 1 and R 2 is independently straight or branched aliphatic, either unsubstituted or substituted with one or more non-interfering substituents; L is a divalent cycloaliphatic group; R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; and (b) inserting said composition in vivo into the peritoneum of said subject, such that the inserted composition is in at least partial contact with an ovarian cancer tumor, wherein the median survival rate of said mammalian subject from said cancer is increased by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

117 . The method of claim 116 wherein a single dose of said polymer composition provides extended release of said antineoplastic agent over a time of at least 28 days.

118 . The method of claim 116 wherein each of R 1 and R 2 is a branched or straight chain alkylene group having from one to seven carbon atoms.

119 . The method of claim 116 wherein each of R 1 and R 2 is a methylene group or an ethylene group.

120 . The method of claim 116 wherein R 3 is an alkoxy group.

121 . The method of claim 116 wherein R 3 is hexyloxy.

122 . The method of claim 116 wherein n is 5 to 500.

123 . The method of claim 116 wherein L is a cycloaliphatic group, either unsubstituted or substituted with a non-interfering substituent.

124 . The method of claim 116 wherein L is cyclohexylene.

125 . The method of claim 92 wherein said polymer is prepared by solution polymerization.

126 . The method of claim 92 wherein said polymer is prepared by melt polymerization.

127 . The method of claim 92 wherein said polymer comprises additional biocompatible monomeric units or is blended with other biocompatible polymers.

128 . The method of claim 92 wherein said polymer is soluble in at least one of the solvents selected from the group consisting of acetone, dimethylene chloride, chloroform, ethyl acetate, DMAC, N-methylpyrrolidone, dimethylformamide and dimethylsulfoxide.

129 . The method of claim 92 wherein said antineoplastic agent comprises paclitaxel.

130 . The method of claim 92 wherein the molecular weight (Mw) of said polymer is from about 2,000 to 400,000 daltons.

131 . The method of claim 92 wherein said antineoplastic agent and said polymer form an amorphous, monolithic matrix.

132 . The method of claim 92 wherein said antineoplastic agent is encapsulated within said polymer.

133 . The method of claim 92 wherein said article results in minimal irritation to non-neoplastic tissues when implanted or injected into vasculated tissue.

134 . The method of claim 92 wherein said composition is a viscous liquid.

135 . The method of claim 92 wherein said composition is formed into a shaped, solid article.

136 . The method of claim 92 wherein said article is in the form of a flexible film, a wafer or a rod.

137 . The method of claim 92 wherein said article is in the form of one or more injectable microparticles.

138 . The method of claim 92 wherein the composition comprises about 5-15% by weight of the antineoplastic agent.

139 . A method for treating a mammalian subject having ovarian cancer, by the extended release of paclitaxel, said method comprising the steps of:
(a) combining the paclitaxel with a biodegradable polymer having the recurring monomeric units shown in formula VI: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; to form a composition; and (b) inserting said composition in vivo into the peritoneum of said subject, such that the inserted composition is in at least partial contact with an ovarian cancer tumor, wherein the median survival rate of said mammalian subject from said cancer is increased by at least about 10%, as compared with the median survival rate obtained by administration of a composition comprising the same dosage of said antineoplastic agent without said biodegradable polymer.

140 . The biodegradable polymer composition of claim 1 , wherein the mammalian subject is a rat or mouse.

141 . The biodegradable polymer composition of claim 44 , wherein the mammalian subject is a rat or mouse.

142 . The solid article of claim 45 , wherein the mammalian subject is a rat or mouse.

143 . The solid article of claim 50 , wherein the mammalian subject is a rat or mouse.

144 . The solid article of claim 91 , wherein the mammalian subject is a rat or mouse.

145 . The method of claim 92 , wherein the mammalian subject is a rat or mouse.

146 . The method of claim 139 , wherein the mammalian subject is a rat or mouse.

147 . A polymer composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula I: wherein X is —O— or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S—, or —NR 4 ; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein the polymer composition is suitable for administration to a mammal, and wherein the polymer composition is in at least partial contact with an ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor.

148 . The polymer composition of claim 147 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

149 . The polymer composition of claim 147 , wherein at least one antineoplastic agent comprises paclitaxel.

150 . The polymer composition of claim 147 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

151 . The polymer composition of claim 150 , wherein at least one antineoplastic agent comprises paclitaxel.

152 . The polymer composition of claim 150 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

153 . The polymer composition of claim 152 , wherein at least one antineoplastic agent comprises paclitaxel.

154 . The polymer composition of claim 147 , wherein said polymer is selected from the group consisting of:

155 . The polymer composition of claim 147 , wherein at least one antineoplastic agent comprises paclitaxel.

156 . The polymer composition of claim 147 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

157 . The polymer composition of claim 156 , wherein at least one antineoplastic agent comprises paclitaxel.

158 . The polymer composition of claim 154 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

159 . A biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula VII: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein the polymer composition is suitable for administration to a mammal, and wherein the polymer composition is in at least partial contact with an ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor.

160 . The polymer composition of claim 159 , wherein said at least one antineoplastic agent comprises paclitaxel.

161 . The polymer composition of claim 159 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

162 . The polymer composition of claim 161 , wherein at least one antineoplastic agent comprises paclitaxel.

163 . The polymer composition of claim 159 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

164 . The polymer composition of claim 160 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

165 . The polymer composition of claim 161 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

166 . The polymer composition of claim 162 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

167 . A biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) the biodegradable polymer shown in formula VI: VI wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein said polymer composition is suitable for administration to a mammal; and wherein the polymer composition is in at least partial contact with an ovarian cancer tumor or the tissue surrounding the tissue that surrounded the site of an ovarian cancer tumor.

168 . The polymer composition of claim 167 , where said at least one antineoplastic agent comprises paclitaxel.

169 . The polymer composition of claim 167 , wherein the polymer composition provides extended release of said paclitaxel for at least about four weeks.

170 . The polymer composition of claim 169 , where said at least one antineoplastic agent comprises paclitaxel.

171 . The polymer composition of claim 167 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

172 . The polymer composition of claim 168 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

173 . The polymer composition of claim 169 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

174 . The polymer composition of claim 170 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

175 . A solid article comprising a biodegradable polymer composition comprising:
(a) at least one antineoplastic agent and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula I: wherein X is -L- or —NR 4 —, where R 4 is H or alkyl; Y is —O—, —S— or —NR 4 —; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein the article is suitable for insertion into a mammal, and wherein the article is in at least partial contact with an ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor.

176 . The article of claim 175 , wherein said antineoplastic agent comprises paclitaxel.

177 . The article of claim 175 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

178 . The article of claim 177 , wherein at least one antineoplastic agent comprises paclitaxel.

179 . The article of claim 175 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

180 . The article of claim 175 , wherein said polymer is selected from the group consisting of:

181 . The article of claim 180 , wherein said antineoplastic agent comprises paclitaxel.

182 . The article of claim 180 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

183 . The article of claim 182 , wherein at least one antineoplastic agent comprises paclitaxel.

184 . The article of claim 180 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

185 . An article comprising a biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) a biodegradable polymer comprising a polymer shown in formula VI: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein the article is suitable for insertion into a mammal; and wherein the article is in at least partial contact with an ovarian cancer tumor or, the tissue surrounding the site of an ovarian cancer tumor.

186 . The article of claim 185 , wherein said antineoplastic agent comprises paclitaxel.

187 . The article of claim 185 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

188 . The article of claim 187 , wherein at least one antineoplastic agent comprises paclitaxel.

189 . The article of claim 185 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

190 . An article comprising a biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula VII: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein the article is suitable for insertion into a mammal; and wherein the article is in at least partial contact with an ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor.

191 . The article of claim 190 , wherein said antineoplastic agent comprises paclitaxel.

192 . The article of claim 190 , wherein the polymer composition provides extended release of at least one antineoplastic agent for at least about four weeks.

193 . The article of claim 192 , wherein at least one antineoplastic agent comprises paclitaxel.

194 . The article of claim 190 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

195 . A biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula IV or V: wherein:
M 1 and M 2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms;
the molar ratio of x:y is about 1;
the molar ratio n:(x or y) is between about 200:1 and 1:200;
the molar ratio q:r is between about 1:99 and 99:1;
X is —O— or —NR 4 —, where R 4 is H or alkyl;
Y is —O—, —S— or NR 4 —; each of R 1 and R 2 is a divalent organic moiety; L is a divalent, branched or straight chain aliphatic group having 1-20 carbon atoms, a cycloaliphatic group, or a group having the formula: R 3 is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is about 5-5,000; wherein the polymer composition is capable of releasing at least one antineoplastic agent in a controlled fashion at the site of a ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor after administration to a mammal.

196 . The polymer composition of claim 195 , wherein said antineoplastic agent comprises paclitaxel.

197 . The polymer composition of claim 195 , wherein at least one antineoplastic is capable of being released for at least four weeks.

198 . The polymer composition of claim 197 , where said antineoplastic agent comprises paclitaxel.

199 . The polymer composition of claim 195 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

200 . The polymer composition of claim 198 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

201 . A biodegradable polymer composition comprising:
(a) at least one antineoplastic agent; and (b) a biodegradable polymer comprising the recurring monomeric units shown in formula VII: wherein the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and n is about 5-5,000; wherein the polymer composition is capable of releasing at least one antineoplastic agent in a controlled fashion at the site of a ovarian cancer tumor or the tissue surrounding the site of an ovarian cancer tumor after administration to a mammal.

202 . The polymer composition of claim 201 , wherein at least one antineoplastic agent comprises paclitaxel.

203 . The polymer composition of claim 201 , wherein at least one antineoplastic is capable of being released for at least four weeks.

204 . The polymer composition of claim 203 , wherein said antineoplastic agent comprises paclitaxel.

205 . The polymer composition of claim 201 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

206 . The polymer composition of claim 204 , wherein the cancer tumor has been removed from the site of an ovarian cancer tumor.

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