Subcutaneous Administration of Amifostine During Fractionated Radiotherapy: A Randomized Phase II Study

Koukourakis, Michael I.; Kyrias, G; Kakolyris, S; Kouroussis, Charalambos; Frangiadaki, Chryssi; Giatromanolaki, Alexandra; Retalis, G.; Georgoulias, V.

doi:10.1200/jco.2000.18.11.2226

Cited by 236 publications

(137 citation statements)

References 21 publications

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“…Studies evaluating the prophylactic use of amifostine during radiotherapy have uniformly reported a reduction of the incidence and severity of oral mucositis, but produced inconsistent results concerning the tolerability of the substanceregardless of its dosage and route of administration. [180][181][182] Similarly, three out of four studies have demonstrated mucosaprotective effects of amifostine during simultaneous radiochemotherapy. [183][184][185][186] Data on the use of amifostine in the prevention of chemotherapy-induced oral mucositis are scant, because the evaluation of mucositis does not constitute a primary endpoint of most studies.…”

Section: Amifostinementioning

confidence: 99%

“…A series of clinical trials have reported on mucosaprotective effects of subcutaneous dosages up to 500 mg and on intravenous use at doses up to 740 mg/m 2 . [180][181][182][183][184][185][186][187][188][189] Side effects, mostly nausea and hypotension, seem to be more pronounced at higher doses and upon intravenous use, whereas, the optimal mucosaprotectant dose and route of administration remains to be defined. Studies evaluating the prophylactic use of amifostine during radiotherapy have uniformly reported a reduction of the incidence and severity of oral mucositis, but produced inconsistent results concerning the tolerability of the substanceregardless of its dosage and route of administration.…”

Section: Amifostinementioning

confidence: 99%

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Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Köstler

Hejna

Wenzel

et al. 2001

CA: A Cancer Journal for Clinicians

294

252

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The incidence and severity of oral mucositis is influenced by the type of antineoplastic treatment administered and by patient-related factors. Severe courses of oral mucositis are observed during simultaneous radiochemotherapy, which Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and TreatmentWolfgang J. Köstler, MD; Michael Hejna, MD; Catharina Wenzel, MD; and Christoph C. Zielinski, MD 290 CA A Cancer Journal for Clinicians ABSTRACT Chemotherapy-and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses.The pathogenesis of this debilitating side effect can be attributed to the direct mucosal toxicity of cytotoxic agents and ionizing radiation and to indirect mucosal damage caused by a concomitant inflammatory reaction exacerbated in the presence of neutropenia, and the emergence of bacterial, mycotic, and viral infections. affects virtually all patients with head and neck cancer who receive this therapeutic modality. 8 However, up to 40% of patients treated with conventional chemotherapy and the more than 70% of patients undergoing conditioning therapy for bone marrow transplantation also experience oral treatment-related complications. 9,10The pathogenesis of oral mucositis is not fully understood, yet it is thought to involve direct and indirect mechanisms. Direct mucosal injury by radiation and chemotherapy interfere with the average 5-to 14-day turnover time of the oral epithelium 11 and induce apoptosis. Indirect stomatotoxic effects that result from the release of inflammatory mediators, loss of protective salivary constituents, and therapyinduced neutropenia have been postulated to contribute to the development of oral mucositis and also promote the emergence of bacteria, fungi, and viruses on damaged mucosa.12 Although a linear relationship among the occurrence of oral mucositis, oral and systemic granulocyte counts, and a coincidence of resolution of mucositis with neutrophil recovery, has been demonstrated, 10,[13][14][15] significant mucositis can occur in the absence of myelotoxicity. 16,17 In addition, the prophylactic or therapeutic elimination of the pathogenic mucosal flora frequently observed in patients developing oral mucositis by various antiseptic and antimicrobial agents can at most alleviate the course of oral mucositis (see Antimicrobal Agents p. 302).Based upon these considerations, newer pathophysiologic concepts have emerged characterizing oral mucositis as having an initial inflammatory/vascular phase, an epithelial phase, a (pseudomembraneous) ulcerative/bacteriological phase and a healing phase.18 During the inflammatory phase, tissue injury induces release of free radicals, modified proteins and proinflammatory cytokines including interleukin-1β, prostaglandins and tumor necrosis factor-α (TNF-α) by epithelial, endothelial, and connective tissue cells. These ...

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Section: Amifostinementioning

confidence: 99%

Section: Amifostinementioning

confidence: 99%

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Köstler

Hejna

Wenzel

et al. 2001

CA: A Cancer Journal for Clinicians

294

252

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“…During the days of radiotherapy (Tuesday to Friday), amifostine was given subcutaneously, as previously described (Koukourakis et al, 2000a). Patients were pretreated with 5 mg of oral Tropisetron (Navoban Ò , Novartis) 1 -2 h before the subcutaneous injection of amifostine.…”

Section: Administration Of Amifostinementioning

confidence: 99%

“…In the present dose escalating study we show that standard radiotherapy can be safely combined with high doses of two drugs, namely Stealth Ò liposomal doxorubicin (Caelyx Ò ) and Docetaxel (Taxotere Ò ), if subcutaneous amifostine is used as a broad spectrum cytoprotective agent (Koukourakis et al, 2000a).…”

mentioning

confidence: 99%

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

et al. 2002

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The substantial augmentation of the radiation sequelae during chemo -radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo -radiotherapy scheme with Stealth Ò liposomal doxorubicin (Caelyx Ò ) and Docetaxel (Taxotere Ò ) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere Ò was 20 mg m 72 week and of Caelyx Ò was 15 mg m 72 every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere Ò /Caelyx Ò was, thereafter, increased to 20/25 (five patients) and 30/25 mg m 72 (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The 'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere Ò / Caelyx Ò chemo -radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the 'in-field' toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer.

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“…Although WR-2721 (amifostine) is the only radioprotector that has been approved by the US Food and Drug Administration at present, it has some severe adverse effects including nausea, vomiting, lethargy, and hypotension with large toxicity (Landauer et al, 1987;Koukourakis et al, 2000). Furthermore, amifostine must be administrated by the intravenous route, which restricts its clinical usage in patients.…”

Section: Introductionmentioning

confidence: 99%

Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage

Wang¹,

Liu²,

Di³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro.

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Subcutaneous Administration of Amifostine During Fractionated Radiotherapy: A Randomized Phase II Study

Cited by 236 publications

References 21 publications

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Oral Mucositis Complicating Chemotherapy and/or Radiotherapy: Options for Prevention and Treatment

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage

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