Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine in patients with malignant pheochromocytoma and paraganglioma - PubMed (original) (raw)

Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine in patients with malignant pheochromocytoma and paraganglioma

Akiyo Tanabe et al. Horm Cancer. 2013 Apr.

Abstract

Choosing effective therapy for patients with malignant pheochromocytoma or paraganglioma (PPGL) is problematic and none of the options are curative. Although combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) is an established treatment option, only a limited number of case series have been reported in the literature. To determine the efficacy of CVD in patients treated at Tokyo Women's Medical University. Retrospective review of patients treated with CVD between 1989 and 2012 was conducted. Demographics, clinical presentation, imaging, and laboratory reports were reviewed and analyzed. Efficacy of CVD was ascertained from the biochemical and tumor responses. Twenty-three patients fulfilled study criteria and 6 of these were excluded due to inadequate follow-up or discontinuance by poor general condition or adverse effects. Thus, 17 cases were included in the study. The age and duration of the disease before initiation of CVD were 54.7 ± 12.0 years and 9.1 ± 8.1 years, respectively. The follow-up period after initiation of CVD ranged from 12 to 192 months (median, 60 months). Complete or partial biochemical and/or partial tumor response was achieved in 47.1 % (responders). No significant biochemical or tumor response was seen in 23.5 % and deterioration in biochemical and tumor outcomes was seen in 29.4 % (non-responders). No patient showed complete biochemical and tumor responses. In responders, these effects were documented within 4 months after initiation of CVD with a progression-free survival of 31 to 60 months (median, 40 months). Age at the first diagnosis with PPGL was younger (P < 0.05) and the lag time to eventual diagnosis of malignant disease was longer (P < 0.05) in responders than those in non-responders. The responders had improvements in hypertension and impaired glucose tolerance. Although CVD chemotherapy is not curative for patients with malignant PPGL, it does provide approximately half of the patients with biochemical, tumor, and hypertension benefits.

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Figures

Fig. 1

Fig. 1

CT before (a) and 2 years after (b) CVD chemotherapy in a patient who showed partial response in a tumor. Arrows show anterior margins of left retroperitoneal tumor mass

Fig. 2

Fig. 2

Clinical course (a) of a patient who showed dissociation between catecholamine levels and MRI findings (b, c). Despite biochemical responses there was no tumor response as measured by MRI. While the findings on 123-I-MIBG (d, e) did correlate with the decline in catecholamine levels during treatment with CVD. The solid line shows urine norepinephrine (in microgram per day) and the dotted line shows plasma norepinephrine (in picogram per milliliter)

Fig. 3

Fig. 3

Box plots (showing median, 25th and 75th percentiles, and an outlier as a closed circle) of age at the first diagnosis of pheochromocytoma (a), age at diagnosis of malignant disease (b), interval between the diagnosis of pheochromocytoma or paraganglioma to the detection of malignant disease (c) and urine norepinephrine level in the patients who were treated with CVD chemotherapy. CR/PR complete or partial response, NC no change, PD progressive disease. *P < 0.05 vs. PD

Fig. 4

Fig. 4

Kaplan–Meier curves which are shown for overall survival in patients with complete or partial biochemical and/or partial tumor response (dashed line), no significant biochemical or tumor response (dotted line) and deterioration in biochemical and tumor responses (solid line)

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References

    1. O’Riordain DS, Young WF, Jr, Grant CS, Carney JA, van Heerden JA. Clinical spectrum and outcome of functional extraadrenal paraganglioma. World J Surg. 1996;20(7):916–921. doi: 10.1007/s002689900139. - DOI - PubMed
    1. Chrisoulidou A, Kaltsas G, Ilias I, Grossman AB. The diagnosis and management of malignant phaeochromocytoma and paraganglioma. Endocr-Relat Cancer. 2007;14(3):569–585. doi: 10.1677/ERC-07-0074. - DOI - PubMed
    1. Mishra AK, Agarwal G, Kapoor A, Agarwal A, Bhatia E, Mishra SK. Catecholamine cardiomyopathy in bilateral malignant pheochromocytoma: successful reversal after surgery. Int J Cardiol. 2000;76(1):89–90. doi: 10.1016/S0167-5273(00)00363-6. - DOI - PubMed
    1. Loh KC, Fitzgerald PA, Matthay KK, Yeo PP, Price DC. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients. J Endocrinol Invest. 1997;20:648–658. - PubMed
    1. Gonias S, Goldsby R, Matthay KK, Hawkins R, Price D, Huberty J, Damon L, Linker C, Sznewajs A, Shiboski S, Fitzgerald P. Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol. 2009;27(25):4162–4168. doi: 10.1200/JCO.2008.21.3496. - DOI - PMC - PubMed

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