Successful treatment of malignant pheochromocytoma with combination chemotherapy containing anthracycline

Abstract

Malignant pheochromocytomas are rare, accounting for ∼10% of all cases of pheochromocytoma. The prognosis is poor because of local recurrence or widespread metastasis [1.van Heerden J.A. Sheps S.G. Hamberger B. et al.Pheochromocytoma: current status and changing trends.Surgery. 1982; 91: 367-373PubMed Google Scholar]. To date, there has been no established chemotherapy for malignant pheochromocytoma. A conventional CVD regimen (consisting of cyclophosphamide, vincristine and dacarbazine) may reduce tumors, but remission is short [2.Averbuch S.D. Steakley C.S. Young R.C. et al.Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.Ann Intern Med. 1988; 109: 267-273Crossref PubMed Scopus (359) Google Scholar]. Thus, attempts to devise other regimens are warranted in order to obtain a better outcome. We report a 50-year-old Japanese male who had rapidly progressive malignant pheochromocytoma and was successfully treated with an ACVD regimen, anthracyclines plus CVD. The patient was diagnosed with left adrenal pheochromocytoma (4 × 3 cm) with increased catecholamine (CA) excretion levels and underwent adrenectomy in August 1990. He had become asymptomatic and CA excretion level dropped to normal after the surgery. Six years later, he presented with lower back pain, soaking sweats and right inguinal lymphadenopathy. CAs and their metabolites were elevated (Table 1). A CT (computed tomography) scan showed enlarged lymph nodes in the pelvic and para-aortic region. Biopsy specimens of the inguinal lymph node revealed relapse of the pheochromocytoma. Subsequently, the right inguinal lymph node enlarged from 2 to 10 cm in ∼2 weeks, and the back pain was aggravated.Table 1Endocrinology data before and after ACVD chemotherapyBefore chemotherapyAfter four cyclesof ACVDNormal rangePlasma catecholamines (pg/ml) Norepinephrine1177422100–450 Epinephrine73<5<100 Dopamine8912<20Urine catecholamines andmetabolites (µg/day) Norepinephrine45110226–121 Epinephrine2133–15 Dopamine300647190–740 Normetanephrine103018070–260 Metanephrine1609050–230 VMA (mg/day)11.94.81.3–5.1Plasma renin activity (ng/ml/h)772.20.3–2.9Plasma aldosterone (pg/ml)2905529.9–159ACVD, anthracyclines plus cyclophosphamide, vincristine and dacarbazine; VMA, vanillyl mandelic acid. Open table in a new tab ACVD, anthracyclines plus cyclophosphamide, vincristine and dacarbazine; VMA, vanillyl mandelic acid. In February 1996, a combination chemotherapeutic regimen was initiated, consisting of doxorubicin 40 mg/m2 body surface area (BSA) on day 1, cyclophosphamide 750 mg/m2 BSA on day 1, vincristine 1.4 mg/m2 BSA on day 1 and dacarbazine 250 mg/m2 BSA on days 1–5, every 3–4 weeks. On the following day, the blood pressure dropped to 90/56 mm Hg. With i.v. hydration increased, his general condition improved within a few days. Symptoms were resolved over 2 weeks with normalization of CAs and their metabolites (Table 1). Since cardiovascular instability occurred, doxorubicin was replaced with epirubicin, which has lower cardiotoxicity, in the later chemotherapy. The patient was given 12 courses of ACVD combination chemotherapy, which led to a complete remission of the tumor and a biochemical response. Side-effects were grade 1 bone marrow suppression, nausea and hair loss. After February 1997, the consolidation CVD regimen was administered monthly for ∼3 years. There has been no sign of recurrence for 3 years after the cessation of chemotherapy. Considering their neural crest origin and biological similarities, the chemotherapeutic regimens for neuroblastoma could be promising candidates for malignant pheochromocytoma. The CVD regimen was based on the treatment for advanced neuroblastoma. This regimen has been reported to produce good responses in malignant pheochromocytoma, but the median duration of remission is 21 months [2.Averbuch S.D. Steakley C.S. Young R.C. et al.Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.Ann Intern Med. 1988; 109: 267-273Crossref PubMed Scopus (359) Google Scholar]. For aggressive neuroblastoma, a combination chemotherapeutic regimen of cyclophosphamide, vincristine, dacarbazine and doxorubicin (CYVADIC) has been suggested to be more effective than doxorubicin alone or combination therapy without doxorubicin (CYVDIC) [3.Dosik G.M. Rodriguez V. Benjamin R.S. Bodey G.P. Neuroblastoma in the adult: effective combination chemotherapy.Cancer. 1978; 41: 56-63Crossref PubMed Scopus (36) Google Scholar]. We achieved long-lasting complete remission using a ACVD regimen in a case with rapidly progressive disease. To our knowledge, this is the first report of an anthracycline-containing combination chemotherapy for metastasized malignant pheochromocytoma. The ACVD regimen might be a feasible combination chemotherapy, with monitoring of the cardiovascular system; furthermore, it might improve response rates and lengthen disease-free survival.