Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel.

BACKGROUND: Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. AIMS: To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. MATERIAL AND METHODS: Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. RESULTS: Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease ≥24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). CONCLUSIONS: The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy.

Anaplastic thyroid carcinoma. Doxorubicin, hyperfractionated radiotherapy and surgery.

Sixteen consecutive patients with anaplastic carcinoma of the thyroid were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin and debulking surgery. The radiotherapy was preoperatively administered to a target dose of 30 Gy in 3 weeks, and postoperatively to an additional dose of 16 Gy in 1.5 weeks. Radiotherapy was administered twice daily, 5 days a week, with a target dose of 1 Gy per fraction and with a minimum interval of 6 hours. A dose of 20 mg doxorubicin was administered intravenously 1 to 2 hours before the first radiotherapy session every week. Debulking surgery was feasible in 9 patients. Local complete remission was achieved in 5 patients and 3 of these are still alive disease-free at 10, 30, and 30 months respectively after diagnosis. Only 6 patients succumbed to a local failure. This combination regimen was well tolerated despite the patients' high age and advanced disease.

Multimodality treatment in anaplastic giant cell thyroid carcinoma.

Anaplastic giant cell thyroid carcinoma is highly malignant. Surgery, chemotherapy, or radiotherapy used separately have not been effective. Combinations of the three modalities have been used at Radiumhemmet since the middle of the 1970s. Nine patients received three-drug chemotherapy and radiotherapy. One patient was alive after 12 years; eight died. Twenty-five patients were given a similar regimen (with two fractions of radiotherapy per day), aiming at surgery. Twelve patients could undergo surgery. Two were alive 11 and 3.5 years after diagnosis. One patient died free of tumor after 6.5 years. Of the remaining 22 patients, many died of metastatic disease. A combination of preoperative and postoperative radiotherapy, chemotherapy (bleomycin, cyclophosphamide, and 5-fluorouracil) and surgery during the remission has given a 12% (four of 34) survival (greater than 3 years). All survivors had undergone surgery. The patients who died had in many cases achieved local tumor control. Adriamycin (Adria Laboratories, Columbus, OH) once a week replaced BCF due to treatment complications in patients receiving BCF. Of five patients, only one was alive more than 10 months after treatment.

Thyroid carcinoma in children and adolescents.

Forty patients aged 20 years or younger at the time of the diagnosis of thyroid carcinoma were followed between 10 and 35 years (mean, 22 years). All patients had had surgery, either a total thyroidectomy or a resection. Sixteen patients received additional radiotherapy. One patient died during surgery. Two patients died of metastatic tumor growth, 5 and 14 years after the primary diagnosis, respectively. Six further patients had recurrences (1-7.5 years after first treatment) and received further treatment. At the end of the study 37 patients were alive without signs of recurrence.

Prognostic impact of nuclear DNA content in medullary thyroid carcinoma; a retrospective pilot study.

The prognostic significance of DNA content in medullary thyroid carcinoma was studied retrospectively in 16 patients. Five patients died within 3 years of medullary thyroid carcinoma and 11 patients survived for at least 10 years. Clinical data and tumour morphology were studied. DNA measurements on tumour cells in histologic sections were performed with slide cytophotometric technique. The tumours of the survivors had in all but two cases a DNA content comparable to that of normal cells, whereas the tumours of the non-survivors and two of the survivors had higher DNA content. The results indicate that DNA measurements in medullary thyroid carcinoma might be of use in addition to clinical and morphologic data and that further studies are warranted.