Ten of 11 patients with ovarian cancer receiving cisplatin developed a distal sensory neuropathy, manifested early by decreased vibratory sensibility in toes and depressed ankle jerks and later by uncomfortable paresthesias. Eleven patients receiving cisplatin, 50 mg/m2 monthly (mean tstal, 580 mg/m2) were studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. Early signs were decreased vibratory sensibility in toes (mean dose, 417 f 132 mg/m2 [SD]) and loss of ankle jerks (mean dose, 455 f 86 mg/m2). With continued therapy, four developed paresthesias. Strehgth was Unaffected. Sural nerve responses abruptly disappeared in six patients (mean dose, 383 +- 103 mg/m2). Other conduction velocities remain4 sormal. Electron microscopy of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown. Platinum concentrations in three patients were similar in tumor (3.3 fig/&, sural nerves (3.5 fig/g), and spinal ganglia (3.8 pg/g), but lower in brain (0.17 fig/&. This may explain the cisplatin toxicity of peripheral nerves with relative sparing of the central nervous system. Cancer 54:1269-1275, 1984. isDiAMiNE DICHLOROPLATINU~~ (cisplatin) has been C used as a cancer chemotherapeutic agent since I 972'.2 and has shown particular efficacy against ovarian, testicular, and bladder cancer^.^ The principle side effects are nephrotoxicity, ototoxicity, nausea and vomiting, and myelos~ppression.~ Scattered reports of peripheral neuropathy associated with cisplatin therapy also have ap~eared.~-'~ The neuropathy was primarily sensory and often the initial symptoms were paresthesias in the feet.4.5.9.10.12.14.15 Mild motor involvement was present in some case^.^.^.' Although most patients improved with cessation of treatment,4,5*10.1 '*13*18 some progressed to severe di~ability.~.~ Previous nerve conduction studies have suggested greater involvement of sensory nerves than motor newes.4.5.9.10.14 Sural nerve biopsies revealed changes interpreted as destruction of myelin in five and

Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies

Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3–4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1–2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of paresthesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6–13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.

Phase I study of oxaliplatin in patients with advanced cancer.

Our institution undertook a phase I trial to define the toxicity of high-dose (150 to 225 mg) bolus administration (every 3 to 4 weeks) of cisplatin in patients with advanced cancers. All patients reported had baseline normal hearing. Hearing levels were measured prior to each course of chemotherapy. Audiological monitoring included conventional assessment of pure tone sensitivity at 500 to 8,000 Hz and assessment of ultra high frequencies (9,000 to 20,000 Hz). After one to two doses, 100% of patients failed to respond at 9,000 Hz and above. In the 2,000 to 8,000 Hz range, repeated administration of the drug effected successively lower frequencies with progressive loss, until a maximum threshold shift or plateau was reached at each frequency between 3,000 and 8,000 Hz. The plateau for cisplatin ototoxicity appears to fall within the moderate hearing loss range (40 to 60 dB HL) in the high frequencies. All patients complained of tinnitus and difficulty understanding speech in the presence of background noise. The pattern of pure tone audiometric alteration is consistent in all patients, all dosages, and each method of administration. The ultra high frequency alteration is prompt and dramatic.

Ototoxicity of high-dose cisplatin by bolus administration in patients with advanced cancers and normal hearing.

Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron or the distal axon was primarily affected, we have carried out serial clinical and electrophysiological studies in 16 males with testicular cancer before or early and late during and after treatment with cisplatin, etoposide and bleomycin at limited ( 400 mg/m2 cisplatin) doses. At cumulative doses of cisplatin higher than 300 mg/m2 the patients lost distal tendon and H-reflexes and displayed reduced vibration sense in the feet and the fingers. The amplitudes of sensory nerve action potentials (SNAP) from the fingers innervated by the median nerve and the dorsolateral side of the foot innervated by the sural nerve were 50-60% reduced, whereas no definite changes occurred at lower doses. The SNAP conduction velocities were reduced by 10-15% at cumulative doses of 400-700 mg/m2 consistent with loss of large myelinated fibres. SNAPs from primarily Pacinian corpuscles in digit 3 and the dorsolateral side of the foot evoked by a tactile probe showed similar changes to those observed in SNAPs evoked by electrical stimulation. At these doses, somatosensory evoked potentials (SEPs) from the tibial nerve had increased latencies of peripheral, spinal and central responses suggesting loss of central processes of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal axonal degeneration even at the lowest toxic doses of cisplatin.

/pdf/neuronal-involvement-in-cisplatin-neuropathy-prospective-2qsxp34zt9.pdf

Neuronal involvement in cisplatin neuropathy: prospective clinical and neurophysiological studies.

Overview of cisplatin-induced neurotoxicity and ototoxicity, and the protective agents.

Peripheral neuropathy developed in two cases of recurrent bladder carcinoma treated with Cis-dichlorodiammineplatinum (II) (DDP) at a dose of 75 mg/m2 IV every 3 weeks. The neuropathy appeared in both patients while they were achieving a subjective and objective response to DDP. The neuropathy was reversible in one patient. In the other patient, a disabling sensory neuropathy progressed despite cessation of therapy. The temporal relationship between the neurological symptoms and the administration of DDP implicate this drug as the possible causative agent in the peripheral neuropathy.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197912%2944%3A6%3C2026%3A%3AAID-CNCR2820440610%3E3.0.CO%3B2-1

Peripheral neuropathy associated with cis-dichlorodiammineplatinum (II) treatment

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.

Dean Hadley

Author Tools

Chat about Author

Papers

Peripheral neuropathy associated with cis-dichlorodiammineplatinum (II) treatment