Aldoxorubicin, a rationally-engineered cytotoxic that delivers doxorubicin to STS by binding to albumin in the bloodstream, is currently in late-stage clinical trials. On October 10, CytRx Corporation, the manufacturer of the drug, presented results of an ongoing Phase 1b/2 trial of aldoxorubicin in combination with mesna and ifosfamide in patients with advanced sarcoma at the European Society for Medical Oncology (ESMO) 2016 Congress held in Copenhagen, Denmark.6
Thirteen of 36 patients (36%) treated with 170 mg/m2 or 250 mg/m2 aldoxorubicin plus ifosfamide achieved a partial response; 22 patients (66%) had stable disease; 1 patient had progressive disease. Dose-limiting toxicities were not observed. Median progression-free survival was not yet reached. The trial was expanded to continue enrollment of additional sarcoma patients at the 250 mg/m2 dose of aldoxorubicin with ifosfamide and mesna. CytRx is aiming to have the therapy approved and commercially available by late 2017.7
In 2012, the FDA approved pazopanib hydrochloride (Votrient), a small-molecule tyrosine kinase inhibitor (TKI), for patients with advanced STS who had received prior chemotherapy.8 The approval was made on the basis of a phase 3 study, even though the improvement in progression free survival was modest, and there was no improvement in overall survival.
A case report published in Oncology Letters in February 2016 describes a case in which a 71-year old patient with leiomyosarcoma who was being treated with pazopanib and radiation suffered a sudden, fatal hemorrhage. The authors recommend that clinicians “be alert” to the possibility of the adverse event.9
While Dr Patel did not speculate on what direction future clinical trials should take, he was optimistic about the possibilities. “It really depends on the drug, its mechanism of action, and what can realistically be expected of it,” he said. “Some can be stand alone options, others need to be combined with non cross-resistant drugs, and still others may be best viewed as supporting cast to the current standard chemotherapy as maintenance.”
- FDA grants accelerated approval to new treatment for advanced soft tissue sarcoma. U.S. Food & Drug Administration website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm525878.htm . Updated October 19, 2016. Accessed October 20, 2016.
- Ratan R, Patel SR. Chemotherapy for Soft Tissue Sarcoma. Cancer. 2016; 122(19):2952-60. doi: 10.1002/cncr.30191
- Treatment of soft tissue sarcomas, by stage. American Cancer Society website. http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-treating-by-stage. Updated February 9, 2016. Accessed October 11, 2016.
- FDA approves new therapy for certain types of advanced soft tissue sarcoma. U.S. Food & Drug Administration website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468832.htm. Updated October 23, 2015. Accessed October 10, 2016.
- FDA approves first drug to show survival benefit in liposarcoma. U.S. Food & Drug Administration website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483714.htm. Updated January 28, 2016. Accessed October 10, 2016.
- CytRx Presents Interim Results from On-going Aldoxorubicin Plus Ifosfamide/Mesna Combination Clinical Trial at ESMO 2016 Congress. CytRx Corporation website. http://phx.corporate-ir.net/phoenix.zhtml?c=187775&p=irol-newsArticle_print&ID=2210440. Updated October 10, 2016. Accessed October 11, 2016.
- Aldoxorubicin – A New Approach to Cancer Treatment. CytRx Corporation website. http://www.cytrx.com/aldoxorubicin. Accessed October 11, 2016.
- FDA Approval for Pazopanib Hydrochloride. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/drugs/fda-pazopanibhydrochloride. Updated July 3, 2013. Accessed October 11, 2016.
- Kawasaki K, Hamamoto Y, Fukada J, et al. Fatal hemorrhage in a patient with advanced soft tissue sarcoma following radiation and pazopanib treatment: A case report. Oncol Lett. 2016;11(4):2408-2410. doi: 10.3892/ol.2016.4246