392 Randomized Phase II study of weekly cisplatin with or without amifostine in patients with advanced head and neck cancer

Planting, A. S. T.; Vermorken, Jan B.; Catimel, G.; Mulder, P.H.M. de; Graeff, Alexander de; Oster, Wolfgang; Verdonk, H.E.R.

doi:10.1016/0959-8049(95)95645-m

Cited by 8 publications

(9 citation statements)

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“…Amifostine reduced the severity of mucositis (P < 0.001), xerostomia (P < 0.001), leukopenia (P ‫ס‬ 0.002), and thrombocytopenia (P ‫ס‬ 0.004) Planting et al [76] 74 adults Pt Randomized ± amifostine…”

Section: Randomized ± Amifostinementioning

confidence: 95%

“…In another trial of adults with head and neck cancer treated with weekly cisplatin, amifostine reduced hypomagnesemia and prevented a cisplatin-induced reduction in creatinine clearance. Furthermore, subclinical neurotoxicity, as assessed by measurement of serial vibration perception threshold (VPT), was reduced significantly in the amifostine group [76]. The effectiveness of amifostine in reducing cisplatin-induced neuropathy has allowed the use of significantly higher mean cumulative cisplatin doses in amifostine recipients compared with controls (635 mg/m 2 vs. 383 mg/m 2 ) [77].…”

Section: Randomized ± Amifostinementioning

confidence: 98%

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Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Bukowski¹

1999

Med. Pediatr. Oncol.

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Section: Randomized ± Amifostinementioning

confidence: 95%

Section: Randomized ± Amifostinementioning

confidence: 98%

Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Bukowski¹

1999

Med. Pediatr. Oncol.

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“…Ex vivo treatment of marrow with amifostine significantly shortened the time to marrow recovery in breast cancer patients receiving high-dose chemo therapy and 4-H C purged autologous bone marrow supportthereby significantly reducing the days of antibiotic therapy and number of required platelet transfusions [10]. Comparable results had been obtained in a trial with lymphoma patients [29], Beside less delays because of bone marrow toxicity and less grade 3/4 thrombocytopenia, an E O R T C randomized phase II study of weekly cisplatin with or without amifostine in patients with advanced head and neck cancer showed nonhematological protection: nephrotoxicity, measured as hypomagnesiemia > grade 2, and ototoxicity grade 2 and 3 were less frequent in the amifostine arm [30]. Furthermore, the incidence of neuropathy was significantly reduced and the mean dose at onset significantly higher in amifostine patients receiving cis platin in combination with other antineoplastic agents [31].…”

Section: Chemoprotectionmentioning

confidence: 74%

“…did not reduce the efficacy of cytotoxic chemotherapy [19,27,28,30,40]; even higher response rates or better survival data have been reported [27,28].…”

Section: Chemoprotectionmentioning

confidence: 99%

Cytoprotection in Chemo – and Radiotherapy with Amifostine (Ethyol): A New Strategy in Oncology

Rieth¹,

Schuth²,

Kudielka³

1996

Oncol Res Treat

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Amifostine (WR-2721, Ethyol), a phosphorylated aminothiol, was originally developed as a radioprotective agent. Since numerous preclinical studies showed that, following dephos-phorylation to the active thiol WR-1065, amifostine selectively protected normal tissues from the damaging effects of irradiation and of several cytotoxic agents without reducing the anti-tumor activity, an intensive clinical development in chemo- and radiotherapy studies was performed. In clinical trials, amifostine proved to be an effective cytoprotector in patients receiving treatment with antineoplastic agents or irradiation. It significantly reduced the incidence and severity of acute, cumulative and delayed toxicities associated with antineoplastic therapy, allowing better patient tolerance of current regimens and possible dose escalation. This protection is achieved without any reduction in the antitumor efficacy. Thus, the integration of amifostine into oncological regimens represents a new ‘preventive’ strategy for a more tolerable and selective therapy.

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“…In the clinical setting, 200 mg m Ϫ2 to 910 mg m Ϫ2 WR-2721 administered in a 15-min infusion, is a tolerable dose when it is combined with anti-emetics and dexamethasone in the higher WR-2721 concentrations. Premedication with 20 mg dexamethasone intravenously and a serotonin receptor antagonist modifies these effects so that only 1% of infusions are associated with WHO grade 3/4 vomiting and less than 1% of patients require infusion interruption for hypotension (Planting et al, 1996). No dexamethasone premedication is necessary at a dose of 200 mg m Ϫ2 amifostine, as used in radiotherapy applications.…”

Section: Wr-2721 Characteristicsmentioning

confidence: 99%

The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects

1999

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Radio- and chemotherapy for the treatment of malignancies are often associated with significant toxicity. One approach to reduce the toxicity is the concomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound recently registered for use in human in many countries, and the natural occurring compound glutathione (GSH). GSH is not registered as a chemoprotective agent. WR-2721 is an aminothiol prodrug and has to be converted to the active compound WR-1065 by membrane-bound alkaline phosphatase. WR-1065 and GSH both act as naturally occurring thiols. No protective effect on the tumour has been found when these compounds are administered intravenously. There is even in vitro evidence for an increased anti-tumour effect with mafosfamide after pretreatment with WR-2721, and in vivo after treatment with carboplatin and paclitaxel. Randomized clinical studies have shown that WR-2721 and GSH decrease cisplatin-induced nephrotoxicity and that WR-2721 reduces radiation radiotherapy-induced toxicity. Side-effects associated with WR-2721 are nausea, vomiting and hypotension, GSH has no side-effects. An exact role of WR-2721 and GSH as chemoprotectors is not yet completely clear. Future studies should examine the protective effect of these drugs on mucositis, cardiac toxicity, neuro- and ototoxicity, the development of secondary neoplasms and their effect on quality of life. © 1999 Cancer Research Campaign

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392 Randomized Phase II study of weekly cisplatin with or without amifostine in patients with advanced head and neck cancer

Cited by 8 publications

References 0 publications

Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Cytoprotection in the treatment of pediatric cancer: Review of current strategies in adults and their application to children

Cytoprotection in Chemo – and Radiotherapy with Amifostine (Ethyol): A New Strategy in Oncology

The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects

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