Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas

Abstract

Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

Keywords: Antineoplastic combined chemotherapy; CVD therapy; Malignant pheochromocytoma; Myelodysplastic syndromes; Paraganglioma; Survival time.

Fig. 1

Kaplan–Meier survival curves in the non-progression and progression groups. a Progression-free survival (PFS). b Overall survival (OS). The PFS and OS in the non-progression group (solid lines; PFS, 1.7 ± 3.3 years; OS, 4.6 ± 3.6 years) were significantly longer than in the progression group (dashed lines; PFS, 0.3 ± 0.3 years; OS, 2.0 ± 3.7 years), as determined by Kaplan–Meier analysis with the log-rank test (χ ² = 16.81; p < 0.001, and χ ² = 6.16; p = 0.01, respectively)

Fig. 2

Kaplan–Meier survival curves in the non-progression and progression groups for a the survival since the first diagnosis of pheochromocytoma/paraganglioma (time after Dx of PPGL) and b since the first diagnosis of metastases (time after Dx of M-PPGL). The durations from the first diagnoses of pheochromocytoma/paraganglioma and malignant disease until follow-up in the non-progression group (solid lines; time after Dx of PPGL, 15.3 ± 7.6 years; time after Dx of M-PPGL, 8.1 ± 4.4 years) were significantly longer than in the progression group (dashed line; time after Dx of PPGL, 5.9 ± 4.1 years; time after Dx of M-PPGL, 2.9 ± 3.6 years), as determined by Kaplan–Meier analysis with the log-rank test (χ ² = 10.04; p < 0.01, and χ ² = 5.49; p = 0.02, respectively)