Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-01-31
2003-12-23
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S455000
Reexamination Certificate
active
06667337
ABSTRACT:
FIELD OF HE INVENTION
This invention relates to a method of treating cancer.
BACKGROUND OF THE INVENTION
The compound 5,6-dimethylanthenone-4-acetic acid PMAA) is known to have significant antitumour activity against murine turmous and human turmours xenografted in immunodeficient mice. Studies have shown that this activity is largely, if not entirely, a consequence of inhibition of blood flow selectively within tumours. However, to date, DMXAA has shown little evidence of clinically viable anti-cancer activity in humans.
The applicants have now surprisingly found that simultaneous or sequential administration of both a compound of the xanthenone acetic acid class (of which DMXAA is one) and either paclitaxel or docetaxel (both compounds of the taxane class of anticancer agents) results in an increase in antitumour activity such that the anticancer effect of the combination is much larger than for either agent alone, and greatly exceeds the sum of effects of the individual agents.
With this background in mind, it was an object of the present invention to provide a method of treatment of cancer which will at least provide the public with a useful choice.
SUMMARY OF THE INVENTION
Accordingly, in a first aspect, the present invention provides a method of treating cancer, the method comprising the step of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a compound selected from paclitaxel and docetaxel, and (ii) a compound of the formula
or a pharmaceutically acceptable salt or ester thereof,
wherein R
1
, R
2
and R3 are each independently selected from the group consisting of H. C
1
—C
6
alkyl, halogen, CF3, CN, NO2, NH2, OH, OR, NHCOR, NHSO
2
R, SR, SO2R or NHR, wherein each R is independently C1—C6 alkyl optionally substituted with one or more substituents selected from hydroxy, amino and methoxy, and wherein each of R1, R2 and R3 may be present at any of the available positions 1 to 8;
and wherein in each of the carbocyclic aromatic rings in formula (I), up to two of the methine (−CH=) groups may be replaced by an aza (−N=) group;
and wherein any two of R
1
, R
2
and R
3
may additionally together represent the group —CH═CH—CH═CH—, such that this group, together with the carbon or nitrogen atoms to which it is attached, forms a fused 6 membered aromatic ring.
Preferably, the mammal is a human.
Preferably, the compound of formula (I) is of the formula:
Most preferably, the compound of formula (I) is 5,6-dimethylxanthenone-4-acetic acid, having the formula
In a further aspect, the present invention provides the use of a compound of the formula (I) as defined above, or a pharmaceutically acceptable salt or ester thereof, in the manufacture of a medicament for treating cancer in a mammal by sequential or simultaneous co-administration of the medicament and a compound selected from paclitaxel and docetaxel.
In still a further aspect, the present invention provides the use of a compound selected from docetaxel and paclitaxel in the manufacture of a medicament for treating cancer in a mammal by sequential or simultaneous co-administration of the medicament and a compound of the formula (I) as defined above or a pharmaceutically acceptable salt or ester thereof.
In yet a further aspect, the present invention provides a pharmaceutical composition suitable for treating cancer, comprising a compound of the formula (I) as defined above or a pharmaceutically acceptable salt or ester thereof, and a compound selected from paclitaxel and docetaxel, in combination with one or more pharmaceutically acceptable carriers or vehicles.
REFERENCES:
patent: 5281620 (1994-01-01), Denny et al.
patent: 5620875 (1997-04-01), Hoffman et al.
patent: 5817684 (1998-10-01), Fleisch et al.
patent: 5910505 (1999-06-01), Fleisch et al.
patent: 2001/0027210 (2001-10-01), Wilson
patent: 0 584 001 (1994-02-01), None
patent: 0 743 064 (1996-11-01), None
patent: 0 584 001 (1997-05-01), None
patent: 2001247459 (2001-11-01), None
patent: WO 94/23753 (1994-10-01), None
patent: WO 95/09621 (1995-04-01), None
patent: WO 97/34482 (1997-09-01), None
patent: WO 98/25600 (1998-06-01), None
patent: WO 98/42332 (1998-10-01), None
patent: WO 98/42335 (1998-10-01), None
patent: WO 98/42336 (1998-10-01), None
patent: WO 98/42337 (1998-10-01), None
patent: WO 98/42346 (1998-10-01), None
patent: WO 98/42650 (1998-10-01), None
patent: WO 00/10600 (2000-03-01), None
patent: WO 00/10600 (2000-03-01), None
patent: WO 00/16798 (2000-03-01), None
patent: 00/48591 (2000-08-01), None
patent: WO 00/76497 (2000-12-01), None
patent: WO 01/34135 (2001-05-01), None
patent: WO 01/34137 (2001-05-01), None
patent: WO 01/34197 (2001-05-01), None
patent: WO 01/34198 (2001-05-01), None
patent: WO 02/09700 (2002-02-01), None
Hill, Sally A. et al, Int. J. Cancer, vol. 63, No. 1, pp. 119-123 (1995).
Chaplin, D.J. et al, Proc. Annu. Am. Assoc. Cancer Res, vol. 37-A3009 (1996).
Pruijin, Frederik B. et al, Cancer Chemother Pharmacol, vol. 39, pp. 541-546 (1997).
Vincent, Patrick W. et al, Oncol. Rep., vol. 4, No. 1, pp. 143-147 (1997).
Combretastatin Updated: Preliminary Results from Ohio Phase 1 Trial Show Tumors Respond, Patients Experience Vascular Stress, PSA Rising: Medical Pike Briefs: Headline Index: Clinical Trial Phase 1 Results, Nov. 8, 1999, available at psa-rising.com/medical/combretastatinupdate.htm.
Kanwar, et al; “Taking lessons from dendritic cells: multiple . . . anti-tumor immunity”; Gene Therapy, 1999; 6: 1835-1844.
Kanwar, et al; “Vascular Attack by 5,6-Dimethylxanthenone-4-acetic Acid . . . Tumors and Multiple Tumor Foci1”, Cancer Resh., 2001; 61: 1948-1956.
Hornung, et al; “Augmentation of Natural Killer Activity, Induction . . . Using Flavone Acetic Acid and IL-21.2”, The Journal of Immunology (1988); vol. 141(10), pp. 3671-3679.
Thomsen, et al; “Nitric Oxide Production in Endotoxin-Resistant . . . Acid Analogues”; Biochem. Pharmacol, 43: 11; 1992; pp. 2401-2406.
Lash, et al; “Enhancement of the anti-tumour effects . . . and ioreductive drugs”; Br. J. Cancer, 78: pp. 439-445, 1998.
Pedley, et al; “Enhancement of Antibody-directed Enzyme . . . by an Antivascular Agent1”, Cancer Res., 59: pp. 3998-4003; 1999.
Pruijn, et al; “Mechanisms of enhancement of the antitumour . . . 5,6-dimethylxanthenone-4-acetic acid”; Cancer Chemother Pharmacol, (1997) 39: pp. 541-546.
Cliffe, et al; “Combining Bioreductive Drugs . . . or 5,6-Dimethylxanthenone Acetic Acid”; Int. J. Rdiation Oncology Biol. Phys., 29: pp. 373-377, 1994.
Phillips; “Inhibition of DT-diaphorase (NAD(P)H:Quinone Oxidoreductase . . . for Bioreductive Drug Development”; Biochem. Pharmacol., 58: pp. 303-310, 1999.
Ching, et al; “Effect of thalidomide on tumour necrosis . . . induced by 5,6-dimethylxanthenone-4-acetic acid”; Br. J. Cancer, 72: pp. 339-343, 1995.
Browne, et al; “Suppression of Serum Tumour Necrosis Factor0&agr; . . . Activity of 5,6-Dimethylxanthenone-4-Acetic Acid”; Anticancer Res., 18: pp. 4409-4414, 1998.
Ching, et al; “Interaction of thalidomide, phthalimide analogues . . . and enhancement of anti-tumour activity”; Br. J. Cancer, 78: pp. 336-343, 1998.
Kestell, et al; “Modulation of the pharmacokinetics of . . . acid (DMXAA) in mice by thalidomide”; Cancer Chemother. Pharmacol., 45: 135-141, 2000.
Cao, et al; “Thalidomide increases both intr-tumoural tumour necrosis . . . in response to 5,6-dimethylxanthenone-4-acetic acid”; Br. J. Cancer, 80: pp. 716-723, 1999.
Baguley, et al; “Serotonin involvement in the antitumour . . . and 5,6-dimethylxanthenone-4-acetic acid”; Br. J. Cancer, 80: pp. 716-723, 1999.
Zwi, et al; “Correlation Between Immune and Vascular Activityes of Xanthenone Acetic Acid Antitumor Agents”; Oncol. Res., 6: pp. 79-85, 1994.
Zhao, et al; Effects of the serotonin receptor antagonist . . . of 5,6-dimethylxanthenone-4-acetic acid (DMXAA); Cancer Chemother. Pharmacol., 47: pp. 491-497, 2001.
Futami, et al; “Cytokine Induction and Therapeutic . . . by Xanthenone-4-Acetic Acid Derivatives”; J. Immunother., 12: pp. 247-255, 1992.
Ching, et al; “Interaction between
Cancer Research Technology Limited
Goldberg Jerome D.
Nixon & Vanderhye
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