A preliminary study of brain gliomas with H17E2 monoclonal antibody: immunoscintigraphy and pharmacokinetics

Ten patients with relapsing high grade brain gliomas and one patient with low grade glioma were studied with a monoclonal antibody (H17E2) against placental alkaline phosphatase. In addition 2 patients with relapsing high grade glioma were studied with a non specific antibody (4D513/2118). 1 mCi of Iodine-131-labelled H17E2 was administered intracarotidly (i.c.) in two, and intravenously (i.v.) in 9 patients. Immunoscintigrams were taken at 0, 2, 24, 48 and 72 hours. Radioactivity was monitored in blood and urine. Tumour/non-tumour ratios were estimated (max. 2.45). All high grade gliomas receiving specific antibody irrespective of the route of administration, gave a positive immunoscintigraphic pattern, increasing in intensity with time. Disappearance of radioactivity in blood was biexpontential with a long component over 30 hours. Urinary excretion of radioactivity ranged from 3.7-21.7% of administered dose/day. The patient with low grade glioma and the patients receiving non specific monoclonal antibody showed a negative pattern, a fast blood clearance and a high urinary excretion. We conclude that a) Iodine-131 labelled H17E2 proved to be stable in vivo and produced satisfactory tumour localisation and b) i.v. route was as good as i.c.     

Immunotargeting of urothelial cell carcinoma with intravesically administered Tc-99m labeled HMFG1 monoclonal antibody

Ten patients with transitional cell carcinoma (TCC) of the bladder received 3–6 mCi of HMFG1 monoclonal antibody (MAb) intravesically. The antibody was labeled with Tc-99m using the 2-Iminothiolane method. All patients underwent transurethral resection of the bladder tumor within 12–20 h following intravesical administration of^99m-Tc-HMFG1. The presence of the radiolabeled MAb in the circulation was studied by measuring the radioactivity in the serum for a period up to 20 h. Three of 10 patients underwent immunoscintigraphy (SPECT) 2–3 h postadministration and cancerous areas could be easily localized. Biopsies were taken from the tumor sites as well as from normal bladder mucosa. Absolute uptake of the administered MAb expressed as percent administered dose/kg of tissue could be evaluated only in eight patients. Multiple specimen taken from various tumor sites in every patient gave a wide range of uptake values ranging from 0 to 9.29% adm. dose/kg, whereas normal tissue uptake values ranged from 0 to 1.63, respectively.     

Ixabepilone Administered Weekly or Every Three Weeks in HER2-Negative Metastatic Breast Cancer Patients; A Randomized Non-Comparative Phase II Trial

To explore the activity and safety of two schedules of ixabepilone, as first line chemotherapy, in patients with metastatic breast cancer previously treated with adjuvant chemotherapy, a randomized non-comparative phase II study was conducted. From November 2008 until December 2010, 64 patients were treated with either ixabepilone 40 mg/m² every 3 weeks (Group A, 32 patients) or ixabepilone 20 mg/m² on days 1, 8 and 15 every 4 weeks (Group B, 32 patients). Overall response rate (the primary end point) was 47% in Group A and 50% in Group B. The most frequent severe adverse events were neutropenia (32% vs. 23%), metabolic disturbances (29% vs. 27%) and sensory neuropathy (12% vs. 27%). Two patients in Group A and 3 in Group B developed febrile neutropenia. After a median follow-up of 22.7 months, median progression-free survival (PFS) was 9 months in Group A and 12 months in Group B. Median survival was 26 months in Group A, whereas it was not reached in Group B. Multiple genetic and molecular markers were examined in tumor and peripheral blood DNA, but none of them was associated with ORR or drug toxicity. Favorable prognostic markers included: the T-variants of ABCB1 SNPs c.2677G/A/T, c.1236C/T and c.3435C/T, as well as high MAPT mRNA and Tau protein expression, which were all associated with the ER/PgR-positive phenotype; absence of TopoIIa; and, an interaction between low TUBB3 mRNA expression and Group B. Upon multivariate analysis, tumor ER-positivity was a favorable (p = 0.0092) and TopoIIa an unfavorable (p = 0.002) prognostic factor for PFS; PgR-positivity was favorable (p = 0.028) for survival. In conclusion, ixabepilone had a manageable safety profile in both the 3-weekly and weekly schedules. A number of markers identified in the present trial appear to deserve further evaluation for their prognostic and/or predictive value in larger multi-arm studies.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 00790894","term_id":"NCT00790894"}}NCT 00790894