- Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. [Journal Article]
- BMBone Marrow Transplant 2018 Jun 15
- The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2, although relatively well ...
The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2, although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose-response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m2 (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial. We report the final long-term outcomes of MM patients who underwent conditioning with MEL 280 with amifostine cytoprotection followed by ASCT. Although the complete response rate was quite high in the era pre-dating the routine use of novel therapies (proteasome inhibitors, immunomodulatory agents) (49%), the progression-free survival was a disappointing 22 months. The implications of this dichotomy between the excellent depth of ASCT response and progression-free survival are discussed.
- Protective Effect of Ginseng on Salivary Dysfunction Following Radioiodine Therapy in a Mouse Model. [Journal Article]
- TThyroid 2018 Jun 15
- CONCLUSIONS: Pretreatment with KRG before RI therapy could be useful to protect against RI induced salivary dysfunction.
- Histologic Improvements in Irradiated Bone Through Pharmaceutical Intervention in Mandibular Distraction Osteogenesis. [Journal Article]
- JOJ Oral Maxillofac Surg 2018 May 19
- CONCLUSIONS: Combined AMF and DFO treatment showed the capacity to remediate the deleterious effects of XRT, restore cellularity to nonirradiated levels, and surpass all groups in mature bone formation. Although further investigations of AMF and DFO are warranted, this study provides preliminary support for the potential use of DO in HNC patients through pharmaceutical facilitation of irradiated bone healing.
- Examination of the effect of ovarian radiation injury induced by hysterosalpingography on ovarian proliferating cell nuclear antigen and the radioprotective effect of amifostine: an experimental study. [Journal Article]
- DDDrug Des Devel Ther 2018; 12:1491-1500
- CONCLUSIONS: In conclusion, amifostine could significantly reduce the ovarian cellular injury induced by HSG.
- Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury. [Journal Article]
- NSNaunyn Schmiedebergs Arch Pharmacol 2018 Jun 02
- Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet be...
Despite the enormous advances made in the field of oncology, no solution to the side effect of nephrotoxicity caused by cisplatin used as an antineoplastic agent for approximately 40 years has yet been discovered. This study investigated the effects of cisplatin on the kidney, the damage mechanism involved, and the potential capacity of agents such as amifostine, curcumin, and melatonin to elicit a future therapeutic protocol in cisplatin-induced nephrotoxicity at the ultrastructural and molecular levels. Our study consisted of five groups: control (saline solution only; group 1), cisplatin (cisplatin only; group 2), cisplatin + amifostine (group 3), cisplatin + curcumin (group 4), and cisplatin + melatonin (group 5). Rats in all groups except the control group were administered a single intraperitoneal dose of 7.5 mg/kg cisplatin. All animals were sacrificed under anesthesia on the sixth day after cisplatin administration. Cisplatin increased serum urea and serum creatinine levels and caused an increase in tubular necrosis scores (TNS), HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). Additionally, we observed basal membrane thickening in glomerules, intense electron deposition in the subendothelial region, and atypical folds in podocyte pedicels. Amifostine, curcumin, and melatonin reduced the increases in serum urea and serum creatinine levels following cisplatin administration and reduced the levels of TNS, HPS, NF-κB/p65, 8-OHdG, and caspase-3 expressions (p < 0.05). ROS-scavenging antioxidants may be a promising means of preventing acute kidney disease in patients using cisplatin in the treatment of malignant tumors.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Radiation esophagitis is inflammation of the esophagitis due to radiation. Radiation esophagitis is typically an adverse effect that develops in individuals receiving radiation cancer therapy, most c...
Radiation esophagitis is inflammation of the esophagitis due to radiation. Radiation esophagitis is typically an adverse effect that develops in individuals receiving radiation cancer therapy, most commonly for breast, lung, and other lymphomas. Symptoms present two to three weeks after initial therapy and include throat pain, dysphagia, and the sensation that food is stuck. Ethyol (amifostine) is a medication used as a radiation protector in selected populations at risk of radiation esophagitis. Typically administered via injection 30 minutes before therapy, patient studies have been promising, showing a reduced risk of developing radiation esophagitis. The goal when treating this condition is adequate nutrition intake, and it is advisable for patients to refrain from eating hot or spicy foods that can further irritate the esophageal lining. In severe cases, perforations, ulcerations, dysmotility, and tracheoesophageal fistulas can be seen. Although there is no cure for radiation esophagitis, symptoms regress 2 to 4 weeks after the completion of radiation treatment.
- Amifostine Analog, DRDE-30, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice. [Journal Article]
- FPFront Pharmacol 2018; 9:394
- Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge ...
Bleomycin (BLM) is an effective curative option in the management of several malignancies including pleural effusions; but pulmonary toxicity, comprising of pneumonitis and fibrosis, poses challenge in its use as a front-line chemotherapeutic. Although Amifostine has been found to protect lungs from the toxic effects of radiation and BLM, its application is limited due to associated toxicity and unfavorable route of administration. Therefore, there is a need for selective, potent, and safe anti-fibrotic drugs. The current study was undertaken to assess the protective effects of DRDE-30, an analog of Amifostine, on BLM-induced lung injury in C57BL/6 mice. Whole body micro- computed tomography (CT) was used to non-invasively observe tissue damage, while broncheo-alveolar lavage fluid (BALF) and lung tissues were assessed for oxidative damage, inflammation and fibrosis. Changes in the lung density revealed by micro-CT suggested protection against BLM-induced lung injury by DRDE-30, which correlated well with changes in lung morphology and histopathology. DRDE-30 significantly blunted BLM-induced oxidative stress, inflammation and fibrosis in the lungs evidenced by reduced oxidative damage, endothelial barrier dysfunction, Myeloperoxidase (MPO) activity, pro-inflammatory cytokine release and protection of tissue architecture, that could be linked to enhanced anti-oxidant defense system and suppression of redox-sensitive pro-inflammatory signaling cascades. DRDE-30 decreased the BLM-induced augmentation in BALF TGF-β and lung hydroxyproline levels, as well as reduced the expression of the mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the suppression of epithelial to mesenchymal transition (EMT) as one of its anti-fibrotic effects. The results demonstrate that the Amifostine analog, DRDE-30, ameliorates the oxidative injury and lung fibrosis induced by BLM and strengthen its potential use as an adjuvant in alleviating the side effects of BLM.
- Corrigendum. [Journal Article]
- JDJ Dent Res 2018 May 01; :22034518774759
- Varghese JJ, Schmale IL, Mickelsen D, Hansen ME, Newlands SD, Benoit DSW, Korshunov VA, Ovitt CE. 2018. Localized delivery of amifostine enhances salivary gland radioprotection. J Dent Res [epub ahea...
Varghese JJ, Schmale IL, Mickelsen D, Hansen ME, Newlands SD, Benoit DSW, Korshunov VA, Ovitt CE. 2018. Localized delivery of amifostine enhances salivary gland radioprotection. J Dent Res [epub ahead of print 10 April 2018] in press. (Original DOI: 10.1177/0022034518767408) In the original online article, the third author's name was misspelled as D. Mickelson. This has been corrected to D. Mickelsen online and in print.
- A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis. [Review]
- TOTransl Oncol 2018; 11(3):771-778
- The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonl...
The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.
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- Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection. [Journal Article]
- JDJ Dent Res 2018 Apr 01; :22034518767408
- Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the ...
Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.