a Department of Pharmaceutical Sciences, School of Pharmacy , Northeastern University , Boston , MA , USA.
b Centre for Nanosciences and Molecular Medicine , Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham , Kochi , India.
Expert Opin Drug Deliv. 2018 May;15(5):481-494. doi: 10.1080/17425247.2018.1446938. Epub 2018 Mar 6.
Epithelial ovarian cancer (EOC) remains to be the most lethal of all gynecological malignancies mainly due to its asymptomatic nature. The late stages are manifested with predominant metastases confined to the peritoneal cavity. Although there has been a substantial progress in the treatment avenue with different therapeutic interventions, the overall survival rate of patients remain poor due to relapse and drug resistance.
The pharmacokinetic advantages offered by intraperitoneal (IP) chemotherapy due to peritoneal-plasma barrier can be potentially exploited for EOC relapse treatment. The ability to retain high concentrations of chemo-drugs with high AUC peritoneum/plasma for prolonged durations in the peritoneal cavity can be utilized effectively through the clinical adoption of drug delivery systems (DDSs) which obviates the need for indwelling catheters. The metronomic dosing strategy could enhance anti-tumor efficacy with a continuous, low dose of chemo-drugs providing minimal systemic toxicity.
The development of a feasible, non-catheter based, IP DDS, retaining the peritoneal-drug levels, with less systemic levels could offer significant survival advantages as a patient-compliant therapeutic strategy. Suturable-implantable devices based on metronomic dosing, eluting drug in a sustained manner at low doses, could be implanted surgically post-debulking for treatment of refractory EOC patients.
上皮性卵巢癌(EOC)仍然是所有妇科恶性肿瘤中最致命的一种,主要是因为其无症状的性质。晚期表现为主要局限于腹腔的转移性疾病。尽管在治疗方法上有不同的治疗干预措施取得了实质性进展,但由于复发和耐药性,患者的总体生存率仍然很差。
由于腹膜-血浆屏障,腹腔内(IP)化疗提供的药代动力学优势可用于治疗 EOC 复发。通过临床采用药物输送系统(DDS),可以有效地利用在腹腔内长时间保持高浓度、高 AUC 腹膜/血浆比的化疗药物,而无需留置导管。节拍式给药策略可以通过持续低剂量的化疗药物提供最小的全身毒性来提高抗肿瘤疗效。
开发一种可行的、非留置导管的、基于 IP 的 DDS,可以保留腹膜药物水平,同时降低全身药物水平,作为一种符合患者要求的治疗策略,可能会带来显著的生存优势。基于节拍式给药的可缝合可植入装置可以在减瘤手术后通过手术植入,用于治疗难治性 EOC 患者。