Vascular complications associated with antineoplastic agents are being reported with increasing frequency. Such vascular toxicity is clinically heterogeneous, ranging from asymptomatic arterial lesions to a fatal thrombotic microangiopathic syndrome. Mitomycin is most commonly implicated in the thrombotic microangiopathic syndrome, while bleomycin, either alone or in combination with a vinca alkaloid or cisplatin, appears to be an important cause of Raynaud's phenomenon. Acute arterial ischemic events, ie, myocardial infarction and cerebrovascular accidents, occur most frequently after cisplatin-based combination chemotherapy. Putative mechanisms for such toxicity include drug-induced endovascular damage, perturbation of the clotting system, platelet activation, an abnormality of thromboxane-prostacyclin homeostasis, autonomic dysfunction, vasculitis, and stimulation of fibroblasts. More than one mechanism may be operative in an individual patient. Better documentation of the incidence and types of vascular toxicity and studies to help elucidate the pathogenesis and management of such toxicity are needed.

Vascular toxicity associated with antineoplastic agents

Background: Paclitaxel administered in combination with a topoisomerase-II inhibitor (such as etoposide) and carboplatin is an effective and safe first-line treatment for patients with small-cell lung cancer (SCLC). We conducted a randomized phase III multicenter trial to determine whether paclitaxel plus etoposide plus carboplatin improves the outcome of patients with primary SCLC relative to standard chemotherapy (carboplatin, etoposide, and vincristine). Methods: Between January 1998 and December 1999, 614 patients with SCLC stages I–IV were randomly assigned to the standard arm (309 patients) or the experimental arm (305 patients). Treatment courses were repeated every 21 days for a maximum of six courses. All patients were evaluated for response rate, survival, and toxicities every two courses. The primary endpoint was survival. Survival curves were estimated with the Kaplan–Meier method and compared using the log-rank test. All statistical tests were twosided. Results: A total of 608 patients were evaluable for all endpoints (standard arm 307 patients, experimental arm 301 patients). The hazard ratio [HR] of death for patients receiving the standard treatment was statistically significantly higher than that for patients receiving the experimental treatment (HR = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P = .024). Progression-free survival was also statistically significantly shorter for patients in the standard arm relative to that of patients in the experimental arm (HR = 1.21, 95% CI = 1.03 to 1.42). There were no differences in the response rates (complete and partial combined) to the treatments (standard arm: 69.4%, 95% CI = 63.9% to 74.5%; experimental arm: 72.1%, 95% CI = 66.7% to 77.1%; difference = 2.7%, 95% CI = 4.5% to 9.9%). Rates of severe grade of anemia, leukocytopenia, neutropenia, and thrombocytopenia were lower in the experimental arm than in the standard arm. Conclusion: Patients with previously untreated SCLC who received paclitaxel, etoposide, and carboplatin showed improved overall and progression-free survival and less frequent hematologic toxicities than those who received the standard therapy. [J Natl Cancer Inst 2003;95: 1118–27]

/pdf/randomized-phase-iii-trial-of-paclitaxel-etoposide-and-58s49maje2.pdf

Randomized Phase III Trial of Paclitaxel, Etoposide, and Carboplatin Versus Carboplatin, Etoposide, and Vincristine in Patients With Small-Cell Lung Cancer

SUMMARY Estracyt, a chemical ester of a nitrogen mustard with estradiol-17/3, was tested for its antiprostatic effects in dogs and rats. Estracyt was shown to interfere with the uptake of labeled estriol by the dog prostate, without affecting that of testosterone and dihydrotestosterone. Similarly, it affected the uptake of estradiol-170 by the prostates of castrated rats, although in this animal it also interfered with the uptake of dihydrotestosterone. Estracyt greatly reduced the prostatic secretion in dogs. The results of these short-term experiments indicate that Estracyt affects a number of different parameters in the prostates of dogs and rats. Possible mechanisms of action of Estracyt were discussed.

Studies on the antiprostatic action of estracyt, a nitrogen mustard of estradiol.

Vascular toxicity following the use of vinblastine, bleomycin, and cisplatin (VBP) combination chemotherapy has been described. This report gives details of five patients who suffered acute life-threatening vascular events following such a chemotherapy regimen for germ cell tumours. In three of the cases no evidence of tumour was found at autopsy. Both acute and long-term vascular toxicity were seen. Large artery vascular disease may result from synergistic toxicity of the drugs comprising the regimen. These cases, with an additional sixteen collected from the literature, suggest that major vascular disease is a significant side-effect of the VBP regimen.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2605.1987.tb00204.x

Vascular toxicity following vinblastine, bleomycin, and cisplatin therapy for germ cell tumours.

Bleomycin-induced lung injury in baboons was investigated by serial bronchoalveolar lavage. Nine juvenile baboons (Papio cynocephalus) were injected intramuscularly with bleomycin sulfate, 1. 5 U/kg body wt., twice weekly for 22 consecutive weeks. Six baboons of similar age served as untreated controls. During the treatment period, the amounts of immunoglobulin G and A and the numbers of eosinophils recovered by bronchoalveolar lavage were increased significantly. Fourteen of the 24 samples from treated animals had ratios of immunoglobulin G or A to albumin which were greater than any corresponding control ratio. After bleomycin was stopped, immunoglobulins G and A and eosinophils returned to control levels. However, during the recovery period lymphocytes were increased significantly in lavage fluids of treated animals for 10 weeks. Immunofluorescence of lung tissue biopsies from treated animals failed to detect immunoglobulins or complement deposition. Similarly, no binding of immunoglobulins present in lavage fluids to normal baboon lung was demonstrated by immunofluorescence. In the presence of collagen peptipes, alveolar macrophages from treated animals migrated shorter distances than did macrophages of control animals. Peripheral blood cells and immunoglobulins were unaffected by bleomycin treatment. These studies suggest that serial bronchoalveolar lavage may aid in the sequential evaluation of patients with diffuse interstitial pulmonary fibrosis, especially when it develops in conjunction with drug therapy.

Bleomycin-induced lung injury in baboons: alteration of cells and immunoglobulins recoverable by bronchoalveolar lavage.

Preclinical toxicologic evaluation of bleomycin (NSC-125066) in rhesus monkeys.

Toxicity in beagle dogs of three alkylating esters with antitumor activity: phenesterin (NSC-104469), estradiol mustard (NSC-112259), and dehydroepiandrosterone mustard (NSC-12121).

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

H Rosenkrantz

Author Tools

Chat about Author

Papers

Preclinical toxicologic evaluation of bleomycin (NSC-125066) in rhesus monkeys.

Toxicity in beagle dogs of three alkylating esters with antitumor activity: phenesterin (NSC-104469), estradiol mustard (NSC-112259), and dehydroepiandrosterone mustard (NSC-12121).