Phase I–II study of pegylated liposomal cisplatin (SPI-077™) in patients with inoperable head and neck cancer

Harrington, Kevin J.; Lewanski, C.R.; Northcote, A.D; Whittaker, J; Wellbank, H; Vile, Richard G.; Peters, A. M.; Stewart, J.S.W.

doi:10.1023/a:1011199028318

Cited by 169 publications

(91 citation statements)

References 7 publications

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“…Three responses (out of 17 patients) were seen with a combination of SPI-77 and vinorelbine in a phase I study (Vokes et al, 2000). In patients with head and neck tumours, it has been administered safely with radiation, but as a single agent was disappointing with no responses (Harrington et al, 2001;Rosenthal et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

et al. 2006

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To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0 -2. The first cohort received SPI-77 at 100 mg m À2 , the second 200 mg m À2 and the final cohort 260 mg m À2 . Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m À2 dose level for an overall response rate of 4.5% (7.1% at X200 mg m À2 ). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

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Section: Discussionmentioning

confidence: 99%

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

et al. 2006

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“…Encapsulation of numerous distinct therapeutic agents has failed to improve their therapeutic profile sufficiently in model systems to warrant clinical development. Others that have progressed to clinical trials have demonstrated limited use (20,21). These observations may reflect the inherent limitations of the encapsulated drug.…”

Section: Introductionmentioning

confidence: 99%

Liposomal Irinotecan

Messerer

Ramsay

Waterhouse

et al. 2004

Clinical Cancer Research

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Purpose:The purpose is to demonstrate whether an appropriately designed liposomal formulation of irinotecan is effective in treating mice with liver-localized colorectal carcinomas.Experimental Design: Irinotecan was encapsulated in 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (55:45 molar ratio) liposomes using an ionophore (A23187)-generated transmembrane proton gradient. This formulation was evaluated in vivo by measuring plasma elimination of liposomal lipid and drug after i.v. administration. Therapeutic activity was determined in SCID/Rag-2M mice bearing s.c. LS180 tumors or orthotopic LS174T colorectal metastases.Results: Drug elimination from the plasma was significantly reduced when irinotecan was administered in the liposomal formulation. At 1 hour after i.v. administration, circulating levels of the liposomal drug were 100-fold greater than that of irinotecan given at the same dose. High-performance liquid chromatographic analysis of plasma samples indicated that liposomal irinotecan was protected from inactivating hydrolysis to the carboxylate form. This formulation exhibited substantially improved therapeutic effects. For the LS180 solid tumor model, it was shown that after a single injection of liposomal irinotecan at 50 mg/kg, the time to progress to a 400-mg tumor was 34 days (as compared with 22 days for animals treated with free drug at an equivalent dose). In the model of colorectal liver metastases (LS174T), a median survival time of 79 days was observed after treatment with liposomal irinotecan (50 mg/kg, given every 4 days for a total of three doses). Saline and free drug treated mice survived for 34 and 53 days, respectively.Conclusions: These results illustrate that liposomal encapsulation can substantially enhance the therapeutic activity of irinotecan and emphasize the potential for using liposomal irinotecan to treat liver metastases.

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“…[114,117] In another clinical studies, liposomal cisplatin formulation (SPI-077) shown a substantial tumor accumulation with almost no anticancer activity due to diffusional limitation of cisplatin through the intact liposomal membrane. [118,119] Active targeting to tumor cells have been envisioned to increase the intracellular delivery and bioavailability of drugs. In recent Phase II clinical trials, actively targeted BIND-014 nanomedicines showed higher accumulation in tumor, yet better therapeutic efficacy was not evidenced.…”

Section: Controlled Drug Releasementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Phase I–II study of pegylated liposomal cisplatin (SPI-077™) in patients with inoperable head and neck cancer

Abstract: SPI-077 is essentially inactive against SCCHN and, in its present formulation, does not merit further evaluation as induction chemotherapy or as part of a CCRT approach.

Cited by 169 publications

References 7 publications

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

Liposomal Irinotecan

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

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