Understanding how to best sequence and combine our new drugs to treat advanced prostate cancer includes the most discussed issue, efficacy. We want to know if a special order or a special combination of the approved drugs will nake a difference in both our quality of life (QoL) as well as how survival. Often left out of this conversation is safety, will the order we take our drugs or in what combination affect the our safety? We know that many of our new drugs cause cross-resistance to the next drug, however we rarely ask about the potential toxic effects that might also develop as a result of the drug sequencing or combinations.
One such issue that has now been evaluated is the sequencing of chemotherapy after the administration of radium-223 (Xofigo). In a sub-analysis of the ALSYMPCA trial it is suggested that chemotherapy can be safely administered after treatment with radium-223in men with metastatic castrate resistant prostate cancer (mCRPC) and bone metastasis.
In a study that was presented at the 18th ESMO-40th ECCO 2015 European Cancer Congress, there was a post-hoc analysis of patients enrolled in ALSYMPCA who received chemotherapy post treatment with radium-223 and post treatment with placebo. The analysis included a 3 year follow-up.
According to the lead study author, Oliver Sartor, M.D., despite some limitations, “this post-hoc analysis indicates that chemotherapy following radium-223 appears to be safe, with no new hematologic concerns and no new detrimental effects on survival. Patients who were earlier in the course of disease and received all 6 injections of radium-223 were able to receive subsequent chemotherapy.
This encouraging finding confirms the flexibility and versatility of radium-223, supporting the safety of administering chemotherapy after radium-223 regardless of prior docetaxel use.”
Of 921 men enrolled in ALSYMPCA, 206 (22%) received chemotherapy post study: 142 from the radium-223 arm and 64 from the placebo arm. Docetaxel was the most commonly used post-study chemotherapy; 70% of the post-radium-223 arm and 72% of the post-placebo arm were treated with docetaxel. Subgroup analysis was performed according to prior docetaxel use.
No significant difference in survival was observed between radium-223 and placebo during or within 30 days of completing chemotherapy. Twenty-nine percent of the men in the radium-223 group and 33% in the placebo group died during and within 30 days of completing chemotherapy. The most common cause of death was prostate cancer (90% in the radium-223 arm and 95% in the placebo arm). Median overall survival (OS) from the start of chemotherapy was 18 months after radium-223 and 15.8 months after placebo, which was not statistically different.
Sartor O, Coleman RE, Nilsson S, et al. 3-year follow-up of chemotherapy following radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients (Pts) with symptomatic bone metastases (Mets) from ALSYMPCA. Presented at: European Cancer Congress 2015; Poster session; Vienna, Austria. Abstract 2510.
– See more at: http://www.targetedonc.com/publications/special-reports/2015/prostate-issue1/chemotherapy-after-radium-223-safe-in-metastatic-castration-resistant-prostate-cancer#sthash.3G15QyX2.dpuf