A phase II, window study of SP1049C as first-line therapy in inoperable metastatic adenocarcinoma of the oesophagus

Abstract

4195 Background: SP1049C is a block co-polymer incorporating doxorubicin resulting in broad in vitro activity and superior anti-tumour activity in 9 out of 9 in vivo animal tumour models compared to doxorubicin. Methods: Chemotherapy- or radiotherapy-naïve patients with measurable, inoperable or metastatic, biopsy-proven, adenocarcinoma of the oesophagus; KP ≥60; normal cardiac LVEF; adequate swallowing and adequate renal, hepatic and bone marrow function were eligible. Treatment: SP1049C 75mg/m2 IV 30-minute infusion was given q3w, for up to 6 cycles. Radiological response was assessed after cycles 2, 4 and 6. Upon disease progression (PD) patients were offered standard chemotherapy. Other assessments included: QoL (by QLQ-C30 and QLQ-OES24 questionnaires), toxicity, disease-related symptoms and cardiac function. Results: From February 2002 to date, 17 male patients; median age 62 years (range 49 – 78); 16 with stage IV disease and 1 unknown stage (TxN1M0); were enrolled. 10 patients are eligible for efficacy analysis. Radiological response after 2 cycles: one (10%) PR, 8 (80%) SD (including 4 (40%) with minor responses) and one (10%) PD. Further partial responses have been seen after cycles 4 and 6 (by investigator assessment) and will be reported in due course. One responding patient underwent salvage resection (pT2N0 (Stage 2A) tumour). Toxicity data is available for 2 cycles for the first 11 patients. Gd 3–4 haematological toxicity (by patient): neutropaenia 8 (73%), leucopaenia 7 (64%), anaemia (0%) and platelets (0%) resulting in six (55%) patients being dose-reduced to 55 mg/m2 at cycle 2. Non-haematological toxicity (Gd1–2,Gd3–4): nausea (73%,0%), anorexia (45%,9%), lethargy (55%,18%), febrile neutropaenia (0%,36%), weight loss (35%,0%), vomiting (45%,18%), mucositis (55%,9%), and Gd 1–2 alopecia in 55%. A significant fall in LVEF (pre-defined as an absolute ≥15% drop from baseline value) was seen in 2 patients. Conclusions: SP1049C appears to be active in advanced oesophageal adenocarcinoma based on the preliminary results of the first 10 patients and the study will continue accrual to a total of 24 evaluable patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Supratek Pharma, Inc. Supratek Pharma, Inc. Supratek Pharma, Inc. Supratek Pharma, Inc.