Agents of the thiazolidinedione drug family can terminally differentiate human liposarcoma cells in vitro by activating genes responsible for lipocyte differentiation. One study has shown clinical activity of troglitazone treatment in liposarcoma patients. We sought to find further evidence for this result. In all, 12 patients with a liposarcoma received rosiglitazone 4 mg b.d. They were followed clinically and with repeated biopsies for histological and biological studies. At the molecular level the mRNA translation of three genes that are induced by this treatment (peroxisome proliferator-activated receptor g (PPARg), adipsin and fatty acid binding protein) was determined. Nine patients were eligible for evaluation. One patient had to stop treatment due to hepatotoxicity. The mean time to progression was 6 months (2 -16 months), with one patient still on treatment. We did not see any significant change in histologic appearance of the liposarcomas by the treatment. The level of gene expression changed significantly in two patients, but this did not result in a clinical response. Based on this study, rosiglitazone is not effective as an antitumoral drug in the treatment of liposarcomas. Increased PPARg activity does not correlate with the clinical evolution.
where collagen IV-positive basement membrane were absent exceeded those in areas where it was present (factor of 1.7) and those in normal mucosa (factor of 1.6). The differences in vessel density between individual tumours and the low variability in vessel density within individual tumours using this quantification technique allow us to investigate the prognostic value of vessel density in areas of intense neovascularisation in human primary colorectal carcinomas.
Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary The aim was to perform a broad phase 11 and pharmacokinetic study of methoxymorpholino-doxorubicin (MMRDX), a drug active against multidrug-resistant tumour cells in vitro when given by i.v. bolus at 1.5 mg m-2 every 4 weeks, in metastatic or unresectable solid tumour patients with known intrinsic drug resistance. Patients received a maximum of six cycles. Plasma, urine and leucocyte MMRDX and its 1 3-dihydro metabolite pharmacokinetic analysis was performed in patients without liver metastases. Patients (n = 48, 21 NSCLC, 19 renal cell, three head and neck tumour, three cervical cancer and two adenocarcinoma of unknown primary) received 132 cycles of MMRDX. Common toxicity criteria (CTC) grade III/IV thrombocytopenia (12% of cycles) and neutropenia (27% of cycles) occurred with median nadir on day 22. Transient transaminases elevation 2 grade III/IV was observed in 7% of cycles, late and prolonged nausea 2 grade 11 in 34% and vomiting . grade 11 in 39%. In two patients, the left ventricular ejection fraction was reduced 2 15%. Of 37 evaluable patients, one out of 17 NSCLC had a partial response. Mean (± s.d.) MMRDX AUCo, calculated up to 24 h after dosing was 20.4 ± 6.2 ,ug h 1-' (n = 11) and tf/2,3 was 44.2 h. Mean plasma clearance (± s.d.) was 37.2 ± 7.3 h-' m-2 and volume of distribution 1982 ± 64 m-2. MMRDX leucocyte levels 2 and 24 h after infusion were 450 to 600-fold higher than corresponding MMRDX plasma levels. In urine, 2% of the MMRDX dose was excreted unchanged, and 2% as metabolite. The main side-effects of 1.5 mg m-2 every 4 weeks of MMRDX are delayed nausea and vomiting and haematological toxicity. MMRDX is characterized by extensive clearance and rapid and extensive distribution into tissues. A low response rate was observed in patients with tumours with intrinsic chemotherapy resistance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.