Data on patients who received recombinant human growth hormone (r-hGH) as children “do not generally support a carcinogenic effect of r-hGH” - although the researchers did see increased risks in certain groups.
In the population-based cohort study of patients in eight European countries, incidence and mortality risks were increased for several cancer sites largely as a result of second primary malignancies in patients who received r-hGH after cancer treatment, the researchers say.
“Cancer mortality in the cohort overall was over 13-fold raised and cancer incidence risk doubled,” they reported online February 10 in the Journal of Clinical Endocrinology and Metabolism.
Odds were significantly increased for both cancer diagnosis and mortality for malignancies of bone, kidney, central nervous system and thyroid. Mortality risk was significantly higher, based on >1 case, for cancers of the tongue, mouth and pharynx, soft tissues, non-Hodgkin lymphoma and leukemia. In addition, there was an elevated incidence of melanoma and ovarian and bladder cancers.
With the exception of bone and bladder cancers, these raised risks were essentially a consequence of risks in patients whose original diagnosis leading to GH treatment was cancer, according to the report.
“There was no clear raised risk in patients with growth failure without other major disease,” the authors wrote. “Only for bone (standardized incidence ratio 2.8) and bladder (SIR 16.3) cancers was incidence significantly raised in GH-treated patients without previous cancer.”
Risk estimates for the major adult cancers, e.g. breast, lung and prostate, had wide confidence intervals, based on few person-years of follow-up.
Follow-up for mortality totaled 396,344 person-years (mean, 16.5 years per patient) and for cancer incidence 154,371 person-years (mean, 14.8 years per patient).
“Cancer risk was unrelated to duration or cumulative dose of r-hGH treatment, but for patients treated after previous cancer, risk of cancer mortality increased significantly with increasing daily r-hGH dose (p trend=0.001 for patients overall and 0.002 for patients without previous cancer),” the authors reported.
They say the “lack of increased risk with greater cumulative dose or duration of treatment … makes a causal relation less likely.” This, along with the lack of a clear raised risk in patients with isolated growth failure, argues “against a major risk of cancer overall within the length of follow-up currently available.”
“This is the biggest and most detailed and longest study in this area so far,” co-author Dr. Gary Butler, of University College London Hospitals, told Reuters Health by email.
The study’s findings are “quite complex to interpret,” Butler said. “All the usual parameters, such as the amount of GH and treatment duration, did not seem to be related to cancer incidence.
“There was a slightly higher cancer risk by dose in those already having had a cancer,” he added. “Bone, bladder and Hodgkins cancer risks did not seem to be related to GH treatment variables, so it’s unclear whether this is a real phenomenon.”
“The current study findings should be interpreted with caution,” given various potential methodological issues, Dr. Sogol Mostoufi-Moab, of The Children's Hospital of Philadelphia, told Reuters Health by email.
To date, she said, multiple reports in the United States “have not shown an increased risk of primary tumor recurrence in childhood cancer survivors treated with GH.”
Prior studies have also shown that “childhood cancer survivors treated with GH appear to have an elevated risk of developing a secondary solid tumor compared to survivors not treated with GH,” she said. Still, she added, “this overall risk remains small and more importantly, it diminishes over time.”
Dr. Mostoufi-Moab, who was not involved in the current study, said this risk should be weighed against GH therapy’s potential benefits for cancer survivors, such as improved final height, increased bone mineral density, reduced frailty, and ameliorated body composition.
“The findings in these studies overall highlight the importance and long-term need for continued surveillance in GH-treated childhood cancer survivors,” she concluded.
The study was funded by the European Union, various national-level organizations and foundations, and Pfizer AG, Novo Nordisk Pharma AG and Sandoz Pharmaceuticals AG.
J Clin Endocrinol Metab 2017.