Radium-223 in combination with paclitaxel in cancer patients with bone metastases: safety results from an open-label, multicenter phase Ib study

Abstract

Purpose Concomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel. Methods Eligible patients had solid tumor malignancies with ≥2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m 2 per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1). Results Of 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast ( n = 7), prostate ( n = 4), bladder ( n = 1), non–small cell lung ( n = 1), myxofibrosarcoma ( n = 1), and neuroendocrine ( n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population. Conclusion Radium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases. Electronic supplementary material The online version of this article (10.1007/s00259-018-4234-6) contains supplementary material, which is available to authorized users.

Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management

“…Because BMs in NEN are predominantly osteoblastic, they could be a good target for radium-223 treatment. Only a phase I study evaluating the safety of radium-223 associated with weekly paclitaxel included one single NEN patient [102]. Thus, clinical studies evaluating the efficacy of radium-223 in NEN patients are urgently needed.…”

A phase IB and randomised phase IIA trial of CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases: CARBON trial results

“…Combinations with chemotherapy are also of interest. A small safety study (n = 15) evaluated the combination of paclitaxel and Ra 223 in a mixed population of cancer patients [11] . The current study is, however, the first to specifically assess Ra 223 in combination with chemotherapy in people with advanced breast cancer.…”

Imaging Biomarkers in Lung Cancer with68Ga-DOTATATE,18F-Fluoride, and18F-FDG PET/CT Scans and the Theranostics Paradigm

“…Reports have also discussed the 177 Lu-DOTATATE treatment paradigm in small cell lung cancer (14)(15)(16)(17). Additionally, some reports and clinical trials are evaluating the benefit of 223 Ra in non-small cell lung cancer (18)(19)(20). One of the prerequisites for 177 Lu treatment is somatostatin receptor expression demonstrated on a companion diagnostic 177 Lu-DOTATATE PET scan such as in our case.…”