The Young Investigator Winner
J. Hadoux1, S. Leboulleux1, A. Al Ghuzlan1, I. Borget1, C. Caramella1, C. Chougnet1, J. Young2, F. Dumont1, F. Deschamps1, M. Schlumberger1 & E. Baudin1
Malignant pheochromocytoma and paraganglioma (PPGLs) are rare diseases with a heterogeneous behaviour. 131I-MIBG therapy and the cyclophosphamide-dacarbazine-vincristine chemotherapy regimen (CVD) constitute the most popular options in the metastatic setting. We have investigated the antitumor effect of temozolomide (TMZ), in patients with metastatic PPGLs. Efficacy was primary endpoint, safety and identification for prognosis factors of response were secondary endpoints.
Fifteen consecutive patients with progressive (n=14) or symptomatic (n=1) metastatic PPGLs received TMZ therapy. There were 12 men (80%); median age was 43 years. Germline mutations were screened: 10 patients harbored SDH B mutation and 5 patients had no mutation. Median number of cycle was 7, mean dose intensity for each cycle was 171 mg/m2 per day (95% CI 160.7181) for five days of a 28-days cycle.
The most frequent all grade toxicities included asthenia, nausea and anemia. Grade three toxicities were lymphopenia (n=2) and hypertension (n=1). According to RECIST 1.1 criteria or F18-FDG-PET evaluation, there was 5 (33%) partial responses, 8 (54%) stable diseases and 2 (13%) progressive diseases. With a median follow up of 29 months (range 6.437.9), median overall survival was not reached and median progression free survival (PFS) was 9.6 months.
Partial responses were observed in 4 out of 10 SDHB mutated patients but in no sporadic case. Patients with SDH B mutations or with no mutation had a median PFS of 16.7 and 2.6 months, respectively (log-rank, P=0.013); Patients with SDH B mutations or with no mutation had a 12-month PFS of 60 or 0% respectively. Methyl guanine methyl transferase (MGMT) expression was analyzed in four patients, including 3 responders and, was found negative.
This study demonstrates for the first time the antitumor efficacy of TMZ in a large series of metastatic PPGLs as well as the potential role for SDH B mutation as a prognosis biomarker of response.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.