Prevention Of Chemotherapy-induced Alopecia Research Articles

Prevention of chemotherapy-induced alopecia in rodent models

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy.

Prevention of chemotherapy-induced alopecia by the anti-death FNK protein

Many anticancer drugs attack rapidly dividing cells, including not only malignant cells but also hair follicle cells, and induce alopecia. Chemotherapy-induced alopecia (CIA) is an emotionally distressing side effect of cancer chemotherapy. There is currently no useful preventive therapy for CIA. We have previously constructed anti-death rFNK protein from rat Bcl-x L by site-directed mutagenesis to strengthen cytoprotective activity. When fused to the protein transduction domain (PTD) of HIV/Tat, the fusion protein PTD (TAT)-rFNK successfully entered cells from the outside in vitro and in vivo to exhibit anti-death activity against apoptosis and necrosis. Here, we show that topical application of FNK protected against CIA in a newborn rat model. The protective activity against hair-loss was observed in 30–1000 nM TAT-rFNK administrative groups in a dose-dependent manner. Furthermore, a human version of FNK (hFNK) fused to other PTD peptides exhibited a protective ability. These results suggest that PTD-FNK possesses protective activity against CIA and is not restricted to a sequence of PTD peptides or species of FNK. Thus, PTD-FNK represents potential to develop a useful method for preventing CIA in cancer patients.

A phase I study to assess the safety and activity of topical lovastatin (FP252S) for the prevention of chemotherapy-induced alopecia

A phase I study was performed to establish the minimum effective dose safety of the topical 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor lovastatin (FP252S) in preventing chemotherapy-induced alopecia in cohorts of three patients receiving their first doses of chemotherapy with doxorubicin (eight patients) or taxanes (four patients). One patient at the first dose level receiving doxorubicin and cyclophosphamide had only grade 1 hair loss at 3 weeks. At dose level 2, one patient on doxorubicin took more than 4 weeks to lose her hair and another on docetaxel retained some hair throughout her chemotherapy. At level 3, one patient had grade 2 hair loss at week 4 and another on docetaxel for 6 cycles showed evidence of hair growth between cycles. There were no grade 3 or 4 toxicities, but at the fourth dose level, no higher concentrations could be formulated. Lovastatin was well-tolerated at the maximum concentration achievable but showed little efficacy.

Expanding research and development of novel agents for the treatment and prevention of chemotherapy-induced alopecia

Chemotherapy-induced alopecia is the most common side effect of medication. This phenomenon is a common patient complaint and a source of significant psychological and physical distress. A major challenge in treating chemotherapy-induced alopecia is to protect the hair without altering the effects of the chemotherapeutic treatment regimen. The search for compounds that can significantly reduce or block damage to the hair follicle by chemotherapeutic agents is an active and dynamic area of research. At present, there are no FDA-approved treatments or preventative measures for chemotherapy-induced alopecia. To address this problem, a variety of new agents have emerged in patent applications. This report reviews 19 patents that have been submitted since 2000 for the treatment or prevention of chemotherapy-induced alopecia.

Prevention of chemotherapy-induced alopecia in rodent models

Prevention of chemotherapy-induced alopecia in rodent models

Effectiveness of the MSC Cold Cap System in the Prevention of Chemotherapy-Induced Alopecia

Objective: To study the effectiveness of the MSC cold cap system to prevent chemotherapy-induced alopecia. Methods: The system was applied in 83 cancer patients (mean age 49.8 years) undergoing chemotherapy with alopecia-causing agents. Seven patients did not tolerate the system. Seventy-six patients were evaluable for assessment; 26 received anthracycline (group A), 33 taxane (group T), 5 anthracycline plus taxane (group AT), 7 intravenous etoposide (group E) and 5 ifosfamide with or without other alopecia-causing drugs (group I). In group A, 18 patients received conventional (subgroup Ac) and 8 high doses (subgroup Ah). In group T, 8 patients received docetaxel (subgroup D) and 25 paclitaxel (subgroup P). Alopecia grade 0–1 (Dean’s system) was considered as treatment success. Results: Grade 0–1 alopecia was achieved in 49/76 (64.5%) patients: group T 23/33 (69.6%), subgroup P 16/25 (64%) and subgroup D 7/8 (87.5%); group A 18/26 (69.2%), subgroup Ac 16/18 (88.8%) and subgroup Ah 2/8 (25%); group AT 1/5 (20%); group E 6/7 (85.7%), and group I 1/5 (20%). Conclusions: The MSC cold cap system is effective in preventing alopecia from anthracycline, etoposide or taxane but not from anthracycline-taxane combinations or ifosfamide-containing regimens.

Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.

Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.

Prevention of chemotherapy-induced alopecia by the new digital scalp cooler device

Prevention of chemotherapy-induced alopecia by the new digital scalp cooler device

Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.

Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.

Prevention of chemotherapy-induced alopecia using an effective scalp cooling system

Alopecia is a distressing side-effect of cancer treatment. Taxanes (TX), anthracyclines (ANR) and etoposide (ET) have been consistently associated with significant alopecia. We studied an effective scalp cooling system, the Penguin Cold Cap system™, for the prevention of chemotherapy-induced alopecia in 70 patients receiving chemotherapy, including one of the following major alopecia-causing agents: Group A, TX-based regimes (without ANR); Group B, TX+ANR; Group C, ANR-based regimes (without TX); Group D, ET-based regimes. Protection from hair loss was achieved by maintaining scalp temperatures below 15°C before, during and after chemotherapy by frequent changing of the caps. Assessment was carried out using a grading system from 0 to 4. Grades 0–2 were considered as satisfactory hair protection, whilst Grades 3–4 were considered failures. 57 patients were evaluable for assessment. An overall 81% protection was achieved. In groups C and D 11 of 12 patients (92%) had no alopecia, whilst 30 of 34 patients (88%) treated with taxanes had adequate hair protection. In Group B, 4 of 11 patients (36%) had adequate hair protection. The system was well tolerated and is a very effective method for protection from hair loss caused by TX, ANR and ET. Our results are comparable with and, in most cases, better than those reported in other studies using various alopecia preventive methods.

Prevention of chemotherapy-induced alopecia using the MSC Cold Cap system

Prevention of chemotherapy-induced alopecia using the MSC Cold Cap system

抗癌剤投与時の脱毛予防に対する試み:－４％食塩水と消毒用エタノールを使用したアイスキャップの冷却効果と脱毛予防効果－

抗癌剤投与時の脱毛予防に対する試み:－４％食塩水と消毒用エタノールを使用したアイスキャップの冷却効果と脱毛予防効果－

The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-I studies, preliminary results from phase-II clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1 RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1 alpha. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Minoxidil (Mx) as a prophylaxis of doxorubicin – induced alopecia

Minoxidil (Mx) is known to induce hair growth in men with male-pattern baldness. Based on this potential, the effectiveness of Mx 2% topical solution was evaluated in cancer patients (pts) to prevent doxorubicin-induced alopecia. 48 female pts with different types of solid tumors treated with doxorubicin-based chemotherapy in a dose range of 50-60 mg/m2/cycle were randomly assigned to receive Mx 2% topical solution or placebo. 88% and 92% of pts in both arms showed severe alopecia (p = ns). No adverse effects were observed. In this study Mx 2% topical solution was non-toxic but was not effective in the prevention of chemotherapy-induced alopecia.

Chemotherapy-induced alopecia: new developments.

Alopecia (hair loss) is one of the most physically and psychologically distressing side effects of cancer chemotherapeutic drugs. Since its first recognition as a common outcome to most chemotherapeutic agents, only a few trials have been reported, using either a method to temporarily reduce the scalp blood flow (scalp tourniquet or hypothermia) or vitamin E, with undocumented and variable efficacy. The lack of progress in the treatment and prevention of chemotherapy-induced alopecia is in part due to the lack of a reproducible animal model. In the past 2 years, we reported on the following observations: (1) treatment of 8-day-old rats with vidarabine (ara-C), doxorubicin, and cyclophosphamide consistently produced either total body alopecia (ara-C and cyclophosphamide) or alopecia confined to the head and proximal part of the back (doxorubicin); (2) Imuvert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against alopecia induced by ara-C and doxorubicin but not that produced by cyclophosphamide; (3) the protective effect of Imuvert against chemotherapy-induced alopecia is mediated by a monocyte-mediated cytokine; and (4) this monocyte-derived cytokine is, possibly, interleukin-1. These observations constitute important progress in the understanding and prevention of chemotherapy-induced alopecia.

Prevention of Chemotherapy-Induced Alopecia by a Hair Grower, Tetaris

Prevention of Chemotherapy-Induced Alopecia by a Hair Grower, Tetaris

Scalp hypothermia in the prevention of chemotherapy-induced alopecia.

Alopecia is a common side effect of cancer chemotherapy, especially in combination with regimens with doxorubicin (Adriamycin). The effect of scalp hypothermia in connection with chemotherapy was evaluated as hair protection in 61 women with disseminated breast carcinoma, where earlier treatment routines had caused wig-requiring alopecia in nearly all patients. The cooling was performed with a gel-helmet (Hypotherm Gel-Kap). Of the 61 patients, 47 (77%) had no or slight, not wig-demanding hair loss, and 14 (23%) had severe (wig-demanding) hair loss. Seven patients had liver dysfunction; in 5 of these severe hair loss was observed; 2 had slight hair loss. Eighty-three per cent of the patients with normal liver function had no hair loss. Treatment tolerance was found to be good, and side effects were minimal. The method is found to be simple, effective and inexpensive, though still not technically optimal.

Prevention of chemotherapy-induced alopecia

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