Trial Of Vincristine Research Articles

228-POS

Objectives We outline a case of a woman with lupus (SLE) and antiphospholipid syndrome (APLA) at 26 weeks’ gestation who develops a complex multiorgan condition with a broad differential. Methods Case report. Results A 34 year old woman, G1P0, presented at 26 weeks gestation with a 5 day history of epigastric pain and emesis. She has a history of lupus anticoagulant (LAC), anticardiolipin (ACL) and anti-dsDNA (ADD) positive SLE and APLA syndrome diagnosed at age 13 with multiple small cerebral infarcts. She was treated with ASA, warfarin and plaquenil; the latter two stopped by age 25, with no recurrent thrombosis. Her pregnancy was conceived through IVF. She continued on ASA and LWMH for prophylactic anticoagulation. Upon presentation, she was hypertensive (pressures >160/100) with thrombocytopenic at 47 × 109/L, creatinine rise from 40 to 93 μmol/L, high uric acid level at 518 μmol/L, and AST and ALT at 74 and 64 U/L respectively peaking in the 4800 s. HIT and SRA were negative, blood films showed schistocytes, positive DAT and C3/C4 levels were low at 0.7 and 0.06 g/L respectively. The patient was diagnosed with preeclampsia and HELLP syndrome. Immediate cesarean section was performed without delivery or hemostatic complications. Placental histology was consistent with preeclampsia. Postpartum, she had persistent severe hypertension with CT confirmed multiorgan infarcts. Anemia and thrombocytopenia also persisted (platelet nadir 4 × 109/L), complement levels remained low and creatinine peak at 485 μmol/L. ADAMTS13 level was 43%. The differential diagnosis included TTP, atypical HUS or SLE progression. High dose steroids, PLEX, dialysis and eculizumab were utilized with minimal response. A trial of vincristine and rituximab was initiated. Conclusions SLE and APLA predispose women to increased pregnancy related complications, including preeclampsia, however the pathogenesis is not well understood. This complex case highlights numerous challenges and addresses the utility of new targeted therapeutic interventions. Disclosures A.E. Lin: None. N. Shehata: None. H. Reich: None. D. Barth: None. C. Laskin: None. S. Lapinsky: None. S. Gandhi: None.

Phase I study of vincristine and escalating doses of etoposide

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.