Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients.
BACKGROUND
A long-term follow-up was conducted of 18 patients with a diagnosis of pheochromocytoma/paraganglioma treated with a combination of cyclophosphamide, vincristine, and dacarbazine (CVD).


METHODS
The study design was a nonrandomized, single-arm trial conducted at a government medical referral center. Eighteen patients with metastatic malignant pheochromocytoma/paraganglioma were studied. After controlling symptoms of catecholamine excess, patients were treated with cyclophosphamide at 750 mg/m(2), vincristine at 1.4 mg/m(2), and dacarbazine at 600 mg/m(2) on Day 1 and dacarbazine at 600 mg/m(2) on Day 2, every 21 to 28 days.


RESULTS
Combination chemotherapy with CVD produced a complete response rate of 11% and a partial response rate of 44%. Median survival from a landmark was 3.8 years for patients whose tumors responded to therapy and 1.8 years for patients whose tumors did not respond (P = .65). All patients with tumors scored as responding reported improvement in their symptoms related to excessive catecholamine release and had objective improvements in blood pressure. CVD was well tolerated with only grade I/II toxicities.


CONCLUSIONS
Combination chemotherapy with CVD produced objective tumor responses in patients with advanced malignant pheochromocytoma/paraganglioma. In this 22-year follow-up there was no difference in overall survival between patients whose tumors objectively shrank and those with stable or progressive disease. However, patients reported improvement in symptoms, had objective improvements in blood pressure, and had tumor shrinkage that made surgical resection possible. The authors conclude that CVD therapy is not indicated in every patient with metastatic pheochromocytoma/paraganglioma, but should be considered in the management of patients with symptoms and where tumor shrinkage might be beneficial.
Huang
Hui
H
Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abraham
Jame
J
Hung
Elizabeth
E
Averbuch
Steven
S
Merino
Maria
M
Steinberg
Seth M
SM
Pacak
Karel
K
Fojo
Tito
T
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D014750:Vincristine; D003606:Dacarbazine; D003520:Cyclophosphamide
Ann Surg. 1974 May;179(5):740-8
4823849
Hypertension. 1997 May;29(5):1133-9
9149678
Surgery. 1982 Apr;91(4):367-73
6801796
J Clin Oncol. 1983 Nov;1(11):710-9
6668489
J Clin Oncol. 2006 Jan 20;24(3):401-6
16421420
Toxicology. 2005 Feb 14;207(2):331-8
15596263
Kidney Int. 1991 Sep;40(3):544-56
1787652
J Clin Endocrinol Metab. 2006 Mar;91(3):827-36
16317055
Surg Gynecol Obstet. 1982 Jun;154(6):801-18
7079921
Anesth Analg. 2000 Nov;91(5):1118-23
11049893
Curr Opin Oncol. 2005 Jan;17(1):13-8
15608506
Aust N Z J Surg. 1985 Oct;55(5):471-5
3868411
Ann Intern Med. 2001 Feb 20;134(4):315-29
11182843
Cancer Res. 2003 Sep 1;63(17):5615-21
14500403
Ann Oncol. 2003 Sep;14(9):1449-51
12954587
Anticancer Drugs. 1997 Jan;8(1):92-7
9147618
Endocr Rev. 1994 Jun;15(3):356-68
8076587
J Clin Endocrinol Metab. 2007 Mar;92(3):779-86
17200167
Mayo Clin Proc. 1983 Dec;58(12):802-4
6645626
Endocr Rev. 2003 Aug;24(4):539-53
12920154
J Hum Hypertens. 1988 Oct;2(3):187-9
3236322
Mayo Clin Proc. 1995 Aug;70(8):757-65
7630214
Ann Thorac Surg. 1999 Aug;68(2):565-6
10475433
Endocr J. 2001 Apr;48(2):151-9
11456261
Cancer Chemother Pharmacol. 1991;28(3):217-9
1855279
J Pediatr Surg. 1968 Feb;3(1):147-8
5655562
J Clin Oncol. 2005 Dec 1;23(34):8812-8
16314641
Ann Surg. 1999 Jun;229(6):755-64; discussion 764-6
10363888
AJR Am J Roentgenol. 2005 Sep;185(3):684-8
16120918
Urology. 1999 Apr;53(4):679-83
10197840
J Clin Endocrinol Metab. 2001 Apr;86(4):1480-6
11297571
Cancer Res. 1987 Nov 1;47(21):5800-5
2822234
Br J Urol. 1985 Aug;57(4):394-8
4027507
Cancer Chemother Rep. 1966 Mar;50(3):163-70
5910392
Medicine (Baltimore). 1991 Jan;70(1):46-66
1988766
Ann Intern Med. 1988 Aug 15;109(4):267-73
3395037
Endocr Relat Cancer. 2004 Sep;11(3):423-36
15369446
Eur J Endocrinol. 1999 Dec;141(6):619-24
10601965
JAMA. 2004 Aug 25;292(8):943-51
15328326
Lancet. 2005 Aug 20-26;366(9486):665-75
16112304
J Clin Endocrinol Metab. 2007 Nov;92(11):4069-79
17989126
World J Surg. 1996 Sep;20(7):916-21; discussion 922
8678971
J Clin Endocrinol Metab. 2006 Nov;91(11):4505-9
16912137
Eur J Surg Oncol. 2003 Apr;29(3):278-83
12657240
Acta Med Scand. 1986;220(3):225-32
3776697
J Intern Med. 1994 Dec;236(6):675-7
7989903
Arch Intern Med. 2000 Oct 23;160(19):2957-63
11041903
J Endocrinol Invest. 1992 Oct;15(9):631-42
1479146
Curr Opin Oncol. 2003 Jan;15(1):84-90
12490767
Radiother Oncol. 1996 Apr;39(1):81-6
8735497