Angiotensin‐Induced Hypertension Chemotherapy in Children with Advanced Solid Tumors

Abstract

Angiotensin‐induced hypertension chemotherapy (IHC) was investigated in six children with the following advanced malignancies: hepatocellular carcinoma, extraskeletal Ewing's sarcoma, sacrococcygeal malignant teratoma, small round cell tumor of the chest wall, hepatoblastoma and osteogenic sarcoma. Partial response was achieved in three of these patients, two showed no change, and in one IHC was used as adjuvant chemotherapy. The side effects of IHC were minimal and tolerable. Angiotensin‐IHC may provide a new approach to pediatric cancer chemotherapy.

Clinical Experience With IV Angiotensin II Administration: A Systematic Review of Safety

“…The majority of subjects received less than or equal to 30 ng/kg/min or a bolus injection of a few micrograms. The highest reported doses were administered in the following settings: one patient with pancreatic cancer (3,780 ng/kg/min) (26); 32 adults with sepsis, systemic inflammatory response syndrome, or liver failure (maximum, 1,600 ng/kg/min; mean, 550 ng/kg/min) (17); two children with septic shock (doses of 160 and 800 ng/kg/min, respectively) (10); seven normal volunteers (100 ng/kg/min) (27); six children with cancer (up to 80 ng/kg/min) (9); and 43 pregnant women (up to 64 ng/kg/min) (7). The duration of infusion was generally minutes to hours although one study applied continuous infusion of ATII at pressor doses for up to 11 days (5).…”

“…ATII was noted to exacerbate the left ventricular failure when administered to three patients with acute congestive heart failure (21). Frequent or severe gastrointestinal AEs occurred only when ATII was coadministered with chemotherapy (9, 35). …”

“…IV ATII has also been administered to patients with a broad range of medical conditions, including cardiovascular, renal, hepatic, and pulmonary diseases, endocrine and metabolic disorders, and traumatic injuries and shock. ATII has also been administered to children with cancer (9), septic shock (10), and congenital cardiac shunts (11). …”

Angiotensin II-induced hypertension enhanced therapeutic efficacy of liposomal doxorubicin in tumor-bearing mice

“…Induced hypertension chemotherapy with intravenously infused AT achieved successful results experimentally and clinically (Fujii et al, 1991;Nagamitsu et al, 2009). AT-induced hypertension selectively enhanced the delivery of 5-fluorouracil (5-FU) in mice bearing mouse sarcoma 180 tumor (Okamoto et al, 1988), and also increased the antitumor effect by combination therapy with 5-FU, doxorubicin and mitomycin C in clinical trials for gastric cancer , advanced carcinoma of the stomach (Nakamura et al, 1992) and advanced gastrointestinal, pancreatic and hepatobiliary carcinoma .…”