Adding cisplatin (CDDP) to imatinib (IM) re-establishes tumor response following secondary resistance to IM in advanced chordoma

Abstract

10038 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The case of a pt with sacral chordoma and lung adenocarcinoma responding to CDDP soon after stopping IM prompted us to combine the two drugs in IM-resistant advanced chordoma. Methods: Since February 2006, 6 advanced chordoma pts (F=4, M=2; mean age 56 yrs; PS 0–2) with a secondary resistance to IM following previous response, have started IM 400 mg/day + low-dose CDDP (25 mg/sqm/wk) on an individual use basis. Results: One pt completed her treatment (after 7 mos, reaching a total dose of CDDP = 525 mg/sqm), and, following ablation of the residual lesion, is now continuing on IM alone. The remaining pts are on combination therapy (4 for <2 mos). After 4–6 weeks, 4 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease on CT/MRI, while 2 were metabolically stable. In the 2 pts treated for >12 weeks, a minor dimensional response was observed after 3 mos. The single pt who completed combination therapy had a continuous PET scan improvement throughout treatment, and pre-ablation biopsy of residual tumor showed histological signs of tumor response (marked cellular depletion and sclerohyalinosis in most of the sample, with residual tumor cells intermingled with inflammatory ones). Conclusions: In 4 out of 6 advanced chordoma pts progressing on IM, a tumor response was re-established by adding CDDP, and 2 pts treated for a relatively longer interval showed dimensional tumor shrinkage. Four more pts are starting therapy, and results will be updated. An independent cytotoxic effect of CDDP cannot be ruled out, but sensitivity of chordoma to CDDP is at best occasional. The combination of IM and CDDP may have synergic activity in chordoma. [Table: see text]