medwireNews: High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective and well-tolerated in patients aged 40 years and older with relapsed metastatic germ cell tumors (GCTs), US researchers report.
Writing in Cancer, Nabil Adra (Indiana University Cancer Center, Indianapolis) and co-authors explain that many healthcare providers “prefer [standard-dose] CT as opposed to HDCT in men ≥40 years of age given the valid concerns for potential toxicity and ability to administer intensive therapy in this older age group.”
However, they say their results show that “[b]eing ≥40 years of age is not an adverse prognostic factor for patients undergoing HDCT plus PBSCT for relapsed GCT.”
Their analysis included 445 patients with metastatic GCT that had progressed after standard cisplatin–etoposide-based combination chemotherapy. Between 2004 and 2017, these individuals received two planned cycles of HDCT with carboplatin and etoposide plus PBSCT and were followed-up for a median 3.5 years.
The researchers report that, at 2 years, the progression-free survival (PFS) rate was 58.7% among the 329 patients who were below 40 years of age (median 28.3 years). This was not significantly different from the 2-year PFS rate of 59.6% among the 116 patients who were aged 40 years or older (median 46.1 years).
There was also no significant difference between the two age groups in 2-year overall survival rates, at 63.9% and 61.5%, respectively.
Multivariable analyses showed that age was not independently associated with outcome, but the risk for disease progression or death was significantly elevated among individuals with an ECOG performance status of 1 or higher (hazard ratio [HR]=1.47), a serum α-fetoprotein level above 1000 ng/mL (HR=1.66), platinum refractory disease (HR=1.69), and a human chorionic gonadotrophin level above 1000 mIU/mL (HR=1.88).
Not completing two cycles of HDCT and having nonseminoma histology were also associated with significantly increased risks for disease progression or death, at HRs of 2.96 and 3.00, respectively.
Moreover, among the individuals with nonseminoma histology (n=347), the 2-year PFS rate was significantly higher in the younger versus older age group, at 52.3% versus 38.1%.
The overall rate of grade 3 or worse nonhematologic adverse events (AEs) was similar between the individuals younger than 40 years of age versus those who were older (18.5 vs 25.0%).
However, the researchers note that younger participants experienced significantly fewer grade 3 or worse renal (2.7 vs 8.6%) and pulmonary (2.4 vs 7.8%) AEs.
Treatment-related mortality rates were 3.0% and 3.5% in the younger and older age groups, respectively.
Adra et al say that their “study demonstrates that select patients ≥40 years of age can be safely treated with HDCT plus PBSCT for relapsed GCT with survival and treatment-related toxicity rates similar to their younger counterparts.”
They add that the findings are “particularly important given recent evidence suggesting an increase in the median age of testicular cancer diagnosis from 28 to 36 years, effectively indicating that optimal treatment strategies for patients ≥40 years of age should be developed.”
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