MANUFACTURING OF TPM SUITABLE FOR HUMAN USE

腹膜癌是美国的主要健康问题。有超过230 000例新的癌症病例是由腹膜腔器官引起的。制药公司通常专注于静脉注射或口服给药的药物。然而，由于肿瘤中血液灌注不足和间质液压力高，全身治疗通常不能向实体瘤递送足够的药物水平。另一方面，腹膜内（ip）化疗在多项NIH资助的随机试验中表现出令人印象深刻的生存优势。由于缺乏批准的ip产品，这些早期研究使用了静脉制剂。这种方法有两个局限性：（a）限制药物渗透到肿瘤周围，降低了ip治疗在较大肿瘤（>1 cm）患者中的疗效，和B）ip治疗与感染（由于留置导管）和高局部药物水平（腹痛）的毒性有关。这些问题阻碍了ip疗法的广泛应用，尽管ip疗法已证明有效。

Peritoneal cancers are major health concerns in the US. There are over 230,000 new cases of cancers arising from organs in the peritoneal cavity. Pharmaceutical companies generally focus on drugs given by intravenous or oral administration. However, systemic therapy often does not deliver sufficient drug levels to solid tumors due to inadequate blood perfusion and high interstitial fluid pressure in tumors. On the other hand, intraperitoneal (ip) chemotherapy has demonstrated impressive survival advantage in multiple NIH-funded randomized trials. Due to the lack of approved ip products, these earlier studies had used intravenous formulations. This approach has two limitations: (a) restricted drug penetration to the tumor periphery diminishes the efficacy of ip treatment in patients with larger tumors (>1 cm), and b) ip therapy is associated with infection (due to indwelling catheter) and toxicity from high local drug levels (abdominal pain). These problems have prevented wide-spread use of ip therapy in spite of the demonstrated efficacy.