There are a few companies currently running trials for the treatment of metastatic soft tissue sarcoma (STS) and other various cancers in combination with the drug Doxorubicin to treat certain types of cancer and other types of soft tissue or bone sarcomas (cancer that forms in muscles and bones). Doxorubicin, is owned by Bedford Laboratories, a division of Boehringer Ingelheim GmbH and is an intravenous (IV) anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug in a class of medications called anthracyclines. It works by slowing or stopping the growth of cancer cells in your body, but response rates are generally low and toxicity can be significant. This is why biotech firms are looking into combo drugs to increase effectiveness and stabilize or extend the lives of cancer victims.
Cancers treated with Doxorubicin include: bladder, breast, head and neck, Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (cancer that begins in the cells of the immune system); and certain types of leukemia (cancer of the white blood cells), including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), liver, lung, mesothelioma, multiple myeloma, neuroblastoma, ovary, pancreas, prostate, sarcomas, stomach, testis (germ cell), thyroid, uterus.
ZIOPHARM Oncology, (ZIOP) - is a biopharmaceutical company focused on the development and commercialization of new cancer therapies and has recently announced the completion of enrollment in its Phase III study of palifosfamide in "combination with doxorubicin" for the treatment of metastatic soft tissue sarcoma in the front-line setting (PICASSO 3).
Palifosfamide (ZIO-201), is a novel DNA-targeted cancer treatment that bypasses drug resistance mediated by ALDH (aldehyde dehydrogenase), an enzyme associated with cancer stem cells, and has a favorable toxicity profile. Intravenous palifosfamide is currently being studied in a randomized, double-blinded, placebo-controlled Phase III trial (PICASSO 3) for the treatment of front-line metastatic soft tissue sarcoma and is also in a pivotal Phase 3 trial (MATISSE) for front-line metastatic small cell lung cancer. Additionally, the Company is developing an oral capsule form of palifosfamide. So far, Palifosfamide has demonstrated "broad therapeutic activity", including effects against cancer stem cells, as well as good tolerability alone and in combination with various chemotherapeutics.
Threshold Pharmaceuticals (THLD) is currently conducting a pivotal Phase III study in soft tissue sarcoma comparing TH-302 in "combination with doxorubicin" against single agent doxorubicin. The same combination regimen of TH-302 with doxorubicin was investigated in the single-arm Phase 2 (TH-CR-403) study. Data from this Phase II study were most recently presented at the Connective Tissue Oncology Society (CTOS) meeting in October of 2011. Also, in February 2011, Threshold Pharmaceuticals announced that it had reached agreement with the U.S. Food and Drug Administration on a Special Protocol Assessment (SPA) for the Phase III study (TH-CR-406) which includes a primary efficacy endpoint of overall survival. The international, randomized, controlled Phase 3 clinical trial was initiated in September 2011, and is being conducted in partnership with the Sarcoma Alliance for Research through Collaboration (SARC). The trial is designed to enroll 450 patients with metastatic or locally advanced unresectable soft tissue sarcoma.
Combining doxorubicin with TH-302 may enable the complementary targeting of both the normoxic and hypoxic regions of soft tissue sarcoma. Combining doxorubicin with TH-302 may enable the complementary targeting of both the normoxic and hypoxic regions of soft tissue sarcoma.
TH-302 was investigated in combination with full-dose doxorubicin as part of a Phase I/II study and the efficacy of the combination was higher than generally reported with single agent doxorubicin. In the Phase II portion of the study, 91 soft tissue sarcoma patients with previously untreated advanced soft tissue sarcoma received 75 mg/m2 doxorubicin in combination with 300 mg/m2 TH-302. Response Evaluation Criteria In Solid Tumors (RECIST) tumor response was available for 89 patients; 2 patients (2%) had a Complete Response (CR); the disappearance of all signs of cancer in response to treatment. 30 patients (34%) had a Partial Response (PR); a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission. And, overall 75 patients (84%) had "stable disease or better" meaning that the cancer did not get any worse! Overall, these were pretty good results.
Summary: Doxorubicin as a single-agent alone is not effective enough for those at risk with various types of cancers including leukemia and soft tissue sarcoma. Combo drugs are the new avenue (bullet) that is currently being developed to deliver better results and a one-two punch to this beast. Expect continued success in these combo trials as they continue to develop strong results.