SP1049C as first-line therapy in advanced (inoperable or metastatic) adenocarcinoma of the oesophagus: A phase II window study

4080 Background: SP1049C (a block co-polymer incorporating doxorubicin) has demonstrated broad in vitro activity and superior anti-tumour activity in 9/9 in vivo animal tumour models compared to doxorubicin. Methods: Chemotherapy- or radiotherapy-naïve patients with measurable, inoperable, recurrent or metastatic adenocarcinoma of the oesophagus; KP ≥60; normal cardiac LVEF; adequate swallowing and adequate renal, hepatic and bone marrow function were eligible. 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. QoL (by QLQ-C30 and QLQ-OES24 questionnaires), toxicity, disease-related symptoms and cardiac function were also prospectively assessed. Results: From February 2002 to December 2004, 21 patients (all male), median age 62 years (range 38–78) with stage 3 (n = 1) of stage IV (n = 20) disease were enrolled. Response rate (WHO criteria) in 19 patients eligible for efficacy analysis (radiologically re-assessed after ≥2 cycles of treatment) included: PR 9/19 (47%), SD (8/19) 42% and PD (2/19) 11% by investigator assessment (confirmed PR 41%, unconfirmed PR 12% and SD 29% by independent review, RECIST criteria). One responding patient underwent salvage resection of a pT2N0 (Stage 2A) tumour. All patients are evaluable for toxicity. Toxicity (Gd 1–2/3–4, by patient) included: neutropaenia 24%/62%, leucopaenia 19%/29%, anaemia 38%/5% and thrombocytopaenia 9.5%/0% (resulting in 9 (43%) patients being dose-reduced to 55 mg/m2 at cycle 2), nausea 81%/19%, vomiting 62%/24%, anorexia 52.4%/14%, lethargy 81%/14%, febrile neutropaenia -/29%, mucositis 48%/5%, and Gd 1–2 alopecia in 67%. Grade I cardiotoxicity (fall in LVEF by 10–19% from baseline, CTC v2.0) was seen in 4 (19%) patients. The median overall survival (all patients) is 10 months; four patients received 2nd-line chemotherapy. Conclusions: SP1049C appears to have activity in monotherapy in this patient group and combination studies with other active agents are warranted. [Table: see text]

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