RESUMO
The safety, pharmacokinetics, biodistribution and radiation dosimetry of (111)In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, were evaluated in a first-in-human trial. Dose escalation was performed in patients with EGFR-positive metastatic breast cancer who had received ≥2 prior courses of systemic treatment. (111)In-DTPA-hEGF (0.25 mg) was administered once intravenously (i.v.). Blood was collected for biochemistry/hematology testing and pharmacokinetic and immunogenicity analyses at selected times post injection (p.i.). Whole body planar images were acquired at 1, 4-6, 24 and 72 h p.i. and SPECT images at 24 and/or 72 h p.i. Macrodosimetry (MIRD) for the whole body and organs was estimated using OLINDA. Correlative radiological imaging was obtained at baseline, 1 and 3 months and then 6 monthly. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE)v2.0. Sixteen patients, median age 47 yr (range, 35-59), received (111)In-DTPA-hEGF as follows: 357-434 MBq (7), 754-805 MBq (3), 1,241-1,527 MBq (3) and 2,030-2,290 MBq (3). Fifteen were evaluable for toxicity. The commonest adverse events (AE) were flushing, chills, nausea, and vomiting occurring during or immediately p.i. One patient experienced Grade 3 thrombocytopenia (attributed to bone marrow infiltration by cancer). There were no other Grade 3 or 4 AEs. Maximum tolerated dose was not reached. Clear accumulation of radiopharmaceutical in at least one known site of disease was observed in 47% of patients. (111)In-DTPA-hEGF was cleared biexponentially from the blood with α-phase T½ of 0.16 ± 0.03 h and ß-phase T½ of 9.41 ± 1.93 h. (111)In-DTPA-hEGF was not immunogenic. The mean radiation dose estimates in mGy/MBq for whole body, liver, kidneys, spleen and thyroid were 0.08, 0.86, 0.74, 0.37 and 0.30, respectively. No objective antitumor responses were observed at the doses studied. In summary, administered amounts of up to 2,290 MBq (0.25 mg) of (111)In-DTPA-hEGF were well tolerated as a single i.v. injection.
RESUMO
PURPOSE: We previously evaluated fatigue, menopausal symptoms, and cognitive dysfunction in patients receiving adjuvant therapy for breast cancer and matched healthy women. Here we report assessment of these women 1 and 2 years later. PATIENTS AND METHODS: Patients without relapse and controls were evaluated by the Functional Assessment of Cancer Treatment-General Quality of Life questionnaire, with subscales for fatigue and endocrine symptoms, and by the High Sensitivity Cognitive Screen. RESULTS: There were 104, 91, and 83 patients and 102, 81, and 81 controls assessed at baseline and at 1 and 2 years, respectively. Median Functional Assessment of Cancer Treatment-Fatigue scores (range, 0 to 52) for patients improved from 31 (on chemotherapy) to 43 and 45 at 1 and 2 years, respectively, but were stable in controls (46 to 48). Median Functional Assessment of Cancer Treatment-Endocrine Symptoms scores (range, 0 to 72) for patients improved from 57 (on chemotherapy) to 59 and 61 at 1 and 2 years, respectively, and were stable in controls (64 to 65). Differences between patients and controls remained significant for these scales. The incidence of moderate-severe cognitive dysfunction by the High Sensitivity Cognitive Screen decreased in patients from 16% (on chemotherapy) to 4.4% and 3.8% and in controls from 5% to 3.6% and 0% at 1 and 2 years, respectively. There were minimal differences between estrogen receptor-positive patients who started hormonal therapy (mainly tamoxifen) after chemotherapy and estrogen receptor-negative patients who did not. Differences in quality of life between patients and controls were significant only at baseline. CONCLUSION: Fatigue, menopausal symptoms, and cognitive dysfunction are important adverse effects of chemotherapy that improve in most patients. Hormonal treatment has minimal impact on them.
