Phase Ib/IIa study of sustained release lipid inhalation targeting cisplatin by inhalation in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung

Abstract

9525 Background: Pulmonary relapse is the most common site of relapse for patients with osteosarcoma (OS). Few therapeutic options are available for these patients. By encapsulating the drug within liposomes, sustained release lipid inhalation targeting (SLIT) cisplatin is a novel sustained-release formulation of cisplatin designed for administration via inhalation, thereby targeting the lungs with little systemic exposure. Methods: A two-center, open-label, phase Ib/IIa study was designed to characterize the safety and efficacy of SLIT cisplatin in patients with OS metastatic to the lung. Two dose levels were utilized: 24 mg/m2/dose, and 36 mg/m2/dose. Study drug was administered via nebulizer once every two weeks. OS patients with only pulmonary relapse were eligible. Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Response was evaluated radiographically according to the World Health Organization criteria after every 2 cycles. When clinically indicated, metastasectomy was undertaken in patients on study after 2 cycles, and levels of SLIT cisplatin were measured in tumor samples upon metastasectomy. Results: Fourteen patients have been treated on study. SLIT cisplatin has been well tolerated in heavily pre-treated patients who have received multiple cycles of therapy, including one patient, approaching cumulative doses of 840 mg of SLIT cisplatin over one year and a second patient receiving 1,020 mg. Specifically, no patients have experienced hematologic toxicity, nephrotoxicity or peripheral neuropathy. Nausea (= grade 3) was attributed to study drug in 5 patients. Respiratory symptoms (= grade 3) were attributable to study drug in 4 patients. No adverse events required discontinuation of study drug. Two patients are pulmonary disease free one year after initiation of therapy. Conclusions: SLIT cisplatin is well tolerated in patients with pulmonary relapse of OS. Two of 14 patients are pulmonary disease free one year after initiation of therapy. SLIT cisplatin provides a novel therapeutic modality for patients with pulmonary relapse of OS, and warrants further study. No significant financial relationships to disclose.

Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma

“…One such strategy is by liposomal encapsulation of drug and aerosolized delivery. Initial phase Ib/IIa study of the sustained release lipid inhalation targeting (SLIT) cisplatin in patients with OS metastatic to the lung has reported to be well tolerated and had pulmonary disease free in two patients (2/14 patients) at one year after start of therapy [ 136 ]. Further clinical study on efficacy of inhaled lipid cisplatin (ILC) in recurrent/progressive metastatic OS patients demonstrated partial response in one and stable disease in two patients (19 patients under evaluation) [ 137 ].…”

Perspectives of the Role of Chemotherapy in the Management of Osteosarcoma

“…A Phase Ib/IIa study of sustained release lipid inhalation targeting cisplatin by inhalation in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung was reported by Chou A. J. Three of eight patients with less bulky disease sustained benefit [57].…”

Αντιμετώπιση Του Καρκίνου Του Πνεύμονα Με Αντινεοπλασματικούς Παράγοντες Χορηγούμενους Διά Των Αεροφόρων Οδών

“…ινη γλσξίδνπκε ηνλ ζπκβαηηθφ ηξφπν ρνξήγεζεο ηεο ρεκεηνζεξαπείαο κε ελδνθιέβηα ρνξήγεζε κε ηηο γλσζηέο παξελέξγεηεο θαη πεξηνξηζκνχο. Βαζηδφκελνη ζε δεκνζηεπκέλεο κειέηεο ζηνλ δηεζλή ηχπν ηέζεθε ην εξψηεκα εάλ ηειηθά ππάξρεη έλαο πην αζθαιήο θαη ίζσο πην απνδνηηθφο ηξφπνο ρνξήγεζεο ηεο ρεκεηνζεξαπείαο 1,2,3,5,9,10,11,12,15,16,20,25,26,27,31 . Θεσξήζεθε ζθφπηκν ζηελ παξνχζα κειέηε λα ρξεζηκνπνηεζεί έλα βαζηθφ ρεκεηνζεξαπεπηηθφ θάξκαθν θαη επηιέρηεθε γηα ηε κειέηε καο ε θαξβνπιαηίλε πνπ έρεη απνδείμεη ηελ απνηειεζκαηηθφηεηα ηεο σο θάξκαθν επηινγήο 1 εο γξακκήο ρεκεηνζεξαπείαο.…”

“…Υεκεηνζεξαπεπηηθέο νπζίεο πνπ ρνξεγήζεθαλ κε ιηπνζσκηαθή κνξθή ήηαλ νη: PTX, DOC, CIS, 5-FU 10,12,15,16,27 . Φάλεθε ζε κειέηε 162 1,2,3,5,9,10,11,12,15,16,20,25,26,27,31 . ηελ παξνχζα κειέηε δηεξεπλήζεθε ν ρεκεηνζεξαπεπηηθφο παξάγνληαο θαξκπνπιαηίλε, θαζψο είλαη έλαο απφ ηνπο πιένλ απνηειεζκαηηθνχο παξάγνληεο ζηελ αληηκεηψπηζε ηνπ θαξθίλνπ ηνπ πλεχκνλα πνπ δελ έρεη ρξεζηκνπνηεζεί ζε άιιεο κειέηεο.…”

“…Ζ ππθλφηεηα CO 2, 5% θξίζεθε ε ηδαληθφηεξε κεηά απφ δνθηκέο κε ππθλφηεηεο απφ 3% έσο θαη 7.5% CO 2 , φπνπ απφ 7.5% θαη πάλσ νη αζζελείο είραλ ζπκπηψκαηα δάιεο θαη ππλειίαο αθφκα θαη δχζπλνηαο, ελψ κε 3% δελ ππήξρε δηαθνξά ζε TV θαη RF 21,29,37 . ηα θξηηήξηα έληαμεο επηιέρζεθαλ αζζελείο κε δηάκεηξν κάδαο απφ 3 έσο 5cm, γηαηί κε βάζε παξφκνηεο δεκνζηεπκέλεο κειέηεο 5,10,26 , αζζελείο κε κεγαιχηεξε κάδα, αθελφο δελ είραλ ην απαξαίηεην ιεηηνπξγηθφ παξέγρπκα ψζηε λα απνξξνθάηαη ηνπηθά επαξθψο ν ρεκεηνζεξαπεπηηθφο παξάγνληαο, θαη αθεηέξνπ παξνπζίαδαλ γξήγνξα αηειεθηαζία. πηξνκέηξεζε έθαλε θάζε αζζελήο πξηλ ηελ εηζπλεφκελε ρεκεηνζεξαπεία θαη κεηά ζε θάζε θχθιν.…”