Low-Dose Oral Minoxidil during Chemotherapy: A Review of the Mechanism and Current Evidence

Abstract

Background

Chemotherapy-induced alopecia (CIA) significantly impacts patients’ quality of life. While low-dose oral minoxidil (LDOM) shows promise in treating CIA after chemotherapy completion, its safety and efficacy when given during active chemotherapy remain unclear. This review examined existing literature on CIA pathogenesis, minoxidil’s mechanism of action, and LDOM efficacy to explore its potential use during chemotherapy.

Summary

Recent retrospective studies demonstrated LDOMs good tolerability in cancer patients post-chemotherapy, with minimal adverse effects. Scalp cooling, the only Food and Drug Administration-cleared intervention to mitigate CIA, is thought to reduce chemotherapeutic delivery to the hair follicles, whereas minoxidil, a vasodilator, increases blood flow to the follicle. Despite these differing mechanisms, preclinical studies suggest potential benefits of LDOM during chemotherapy. One study demonstrated a protective effect of subcutaneous minoxidil against cytarabine-induced alopecia, while another showed faster regrowth with systemic minoxidil administered concurrently with paclitaxel. LDOM may, therefore, exert benefits through mechanisms beyond vasodilation, potentially by its impact on the hair cycle. Studies on topical minoxidil during chemotherapy show variable results, possibly due to poor adherence or variations in application practices – limitations LDOM could address.

Key Messages

Given the psychological impact of CIA and limited treatments, investigation of LDOM’s safety and efficacy when initiated during chemotherapy is warranted.

Introduction

Chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects (AEs) of cancer treatment, leading some patients to consider declining potentially curative treatment due to concerns about hair loss [1, 2]. The significant impact of CIA on a patient’s quality of life highlights the need for effective strategies to reduce hair loss during chemotherapy and to support hair regrowth after treatment concludes. Low-dose oral minoxidil (LDOM) has emerged as a promising treatment for CIA, although most studies focus on initiating LDOM after chemotherapy is completed [3–5]. The safety and efficacy of initiating LDOM during chemotherapy, rather than waiting until anti-cancer treatment is complete, remains unclear.

While direct clinical evidence for LDOM use during chemotherapy does not yet exist, this review brings together multiple lines of evidence, including CIA pathogenesis, minoxidil’s mechanism of action, safety data from related contexts, and studies on topical minoxidil during chemotherapy, to establish a foundation for future studies. Currently available evidence primarily consists of animal studies investigating the use of subcutaneous or systemic minoxidil during chemotherapy and small randomized clinical trials (RCTs) assessing safety and efficacy of topical minoxidil during chemotherapy [6–10]. This review aimed to synthesize existing literature to establish a rationale for investigating LDOM during chemotherapy, addressing a critical gap in current treatment options for CIA.

Overview of CIA

Chemotherapy reaches hair follicles through the bloodstream, as the follicle’s rich vascular network makes it particularly vulnerable to drug exposure [11]. Different chemotherapy agents have varying degrees of penetration into the hair follicle based on their molecular properties and typical treatment doses [11]. As such, the major classes of cytotoxic chemotherapy carry differing risks of CIA: topoisomerase inhibitors have the highest incidence of CIA at 60–100%, followed by microtubule inhibitors (80%), alkylating agents (60%), and antimetabolites (10–50%) [12].

The anagen (growth) phase of the hair cycle is characterized by increased blood flow and metabolic activity at the hair follicle [13, 14]. This makes actively growing follicles the most susceptible to chemotherapy [13, 14]. These agents induce alopecia by damaging the highly proliferative matrix keratinocytes in the hair bulb [13]. The resulting alopecia generally manifests as anagen effluvium and begins 1–3 weeks after starting chemotherapy [13, 15]. The hair shafts in patients with CIA exhibit dystrophic structural changes with constriction points prone to hair breakage, coinciding with drug exposure [13].

Automated scalp cooling (SC) systems are the only intervention cleared by the Food and Drug Administration (FDA) to mitigate CIA [16, 17]. SC is thought to cause vasoconstriction of the scalp blood vessels, reduce uptake of chemotherapy by the hair follicle, and lower the intrafollicular metabolic rate [16]. It is approximately 60% effective in retaining more than half of hair, though this varies based on chemotherapy regimen [18]. Automated SC systems have been found to be more effective in preventing CIA in breast cancer (BC) patients receiving taxane-based regimens compared to those receiving anthracycline-based regimens [19]. Thus, continued research into preventative therapies that minimize CIA and restorative therapies that promote hair regrowth after chemotherapy is needed.

Overview of Minoxidil Mechanism of Action

Minoxidil is a peripheral vasodilator developed as a treatment for hypertension and was incidentally noted to increase hair growth [20]. This finding led to its repositioning at lower doses as medical therapy for various forms of alopecia, which maintains the benefits for hair regrowth while mitigating potential drug-related AEs [20]. Minoxidil is converted to its active form, minoxidil sulfate, by the enzyme sulfotransferase 1A1, which is expressed in the hair follicle outer root sheath [21]. Minoxidil sulfate is believed to activate adenosine triphosphate-sensitive potassium channels in the vascular smooth muscle and the hair follicle dermal papilla, promoting vasodilation and increased microcirculation at the follicle [20]. Secondary mechanisms of action include upregulation of vascular endothelial growth factor signaling and prostaglandin synthesis, also increasing local circulation [21]. Minoxidil may shorten the telogen phase of the hair cycle, triggering an early shift into the anagen phase [22]. It may also extend the anagen phase, contributing to increased hair length and thickness [22].

LDOM during Chemotherapy: Safety

To advocate for the use of LDOM during chemotherapy, one must first establish its safety profile in this population. LDOM (≤5 mg daily) is generally well-tolerated, with a lower incidence of AEs compared to its use at higher doses for hypertension [23]. A large multicenter retrospective review on the safety of LDOM in treating alopecia found the most frequent AE to be hypertrichosis in 15% [24]. Additional AEs included lightheadedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), and periorbital edema (0.3%) [24]. All AEs resolved after minoxidil dose adjustment or withdrawal [24]. Several recent studies have found no clinically significant impact of LDOM on blood pressure (BP) in alopecia patients, including those with a history of abnormal BP and using other BP-lowering medications [25–27].

Although there are no direct studies investigating LDOM in cancer patients during chemotherapy, recent retrospective reviews of cancer patients who received LDOM after completing treatment demonstrated good tolerability [3–5]. A 2024 retrospective study that evaluated LDOM for various types of alopecia in 25 BC patients reported no severe AEs, including in patients who received cardiotoxic chemotherapy [5]. The most frequent AEs were hypertrichosis in 50% of patients, edema in 22%, and tachycardia in 11% [5]. Another 2024 retrospective review of 55 patients with CIA or endocrine therapy-induced alopecia (EIA) receiving combination therapy with LDOM and topical minoxidil 5% found overall low incidences of hypertrichosis (13.5%), edema (5.4%), palpitations (2.7%), and headache and dizziness (2.7%) [3]. The median time from chemotherapy completion to alopecia diagnosis in this study was 39 months (range 13.3–139.5 months) in patients with persistent CIA (pCIA), defined as incomplete hair regrowth 6 months or more after concluding chemotherapy, and 25.3 months (range 14.5–151.0 months) in those with both pCIA and EIA [3]. Finally, a larger review of 216 patients with pCIA or EIA found no documentation of AEs attributed to LDOM [4].

Importantly, all three studies reported that no patient experienced serious cardiovascular AEs, such as cardiopulmonary edema, after LDOM treatment durations of mean 7.6 months (range 0.2–57.5 months), mean 20.3 months (standard deviation 17.9 months), and median 105 days, or approximately 3.5 months (interquartile range 70 days or approximately 2.3 months), respectively [3–5]. Establishing the safety of LDOM with respect to cardiovascular AEs in patients undergoing chemotherapy is critical, especially considering the potential comorbidity conferred by treatment with cardiotoxic chemotherapy agents [5]. Although no studies have evaluated LDOM tolerability during chemotherapy, other medications with vasodilatory effects, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers, are commonly used to manage hypertension during cancer treatment with minimal AEs, suggesting LDOM may be similarly well-tolerated [28]. Multiple meta-analyses investigating the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers in cancer patients have found either no significant impact or improvement in disease-free and overall survival [29–33]. Current evidence suggests LDOM has no clinically significant impact on BP, including those already on other antihypertensives, and this concomitant literature documenting the safe use of other vasodilatory medications in cancer patients lends further support for the potential safety of LDOM in this population.

In addition, preclinical studies have highlighted possible anti-metastatic and anti-proliferative benefits of minoxidil in various cancer cell lines, including breast, endometrial, and ovarian cancers [34, 35]. One study examined the effects of minoxidil on cell invasion in two triple-negative BC cell lines and found dose-dependent anti-invasive effects [34]. Another study demonstrated that minoxidil could arrest tumor growth in ovarian cancer xenograft models [35]. These anti-metastatic and anti-proliferative effects are thought to be linked to minoxidil's action on adenosine triphosphate-sensitive potassium channels, such as the Kir6.1/SUR2 channel [34, 35]. Specifically, minoxidil was shown to inhibit cell proliferation and alter the metabolic state of Kir6.1/SUR2-positive ovarian cancer cell lines, increasing intracellular reactive oxygen species levels and triggering caspase-3-independent apoptosis [35]. There is currently no evidence to support the use of minoxidil as a treatment for cancer, but these preclinical findings do at the very least suggest that LDOM is unlikely to worsen oncologic outcomes in cancer patients.

There are currently no studies that investigate pharmacokinetic or pharmacodynamic interactions between minoxidil and chemotherapeutic agents. Most chemotherapies have no known medication interactions with systemic minoxidil (Table 1). Paclitaxel and minoxidil co-administration may increase the risk of hypotension (Table 1) [36]. From a theoretical pharmacodynamic perspective, the potential fluid retention or BP-lowering effect of systemic minoxidil could exacerbate similar effects seen with multiple classes of chemotherapy (Table 1) [37]. This theoretical risk may be heightened in patients with pre-existing cardiac comorbidities or reduced cardiac function. One retrospective study found that oral minoxidil at 5 mg daily has the potential to worsen fluid retention in patients with systemic diseases impacting the heart and kidneys, such as systemic lupus erythematosus [38]. The use of LDOM at doses less than 5 mg daily is common in alopecia treatment. Lower doses may help mitigate the potential for additive cardiovascular effects [24]. Additional research is needed to assess potential pharmacological interactions between minoxidil and common chemotherapy regimens.

Table 1.

Cardiotoxicities associated with common chemotherapy classes and known medication interactions between chemotherapy agents and systemic minoxidil

Class	Potential cardiotoxicity	Agent	Known medication interactions with minoxidil (oral)	References
Alkylating agents	Cardiomyopathy, arrhythmia, arterial vascular disease, HTN	Cyclophosphamide	None	Lexidrug Interactions Database [36], Herrmann 2020 [37], Morelli 2022 [39]
		Ifosfamide	None
		Melphalan	None
		Chlorambucil	None
		Busulfan	None
		Carmustine	None
		Lomustine	None
		Dacarbazine	None
		Temozolomide	None
		Thiotepa	None
Platinum-based compounds	Arterial vascular disease, venous thromboembolism, systemic hypertension	Cisplatin	None	Lexidrug Interactions Database [36], Herrmann 2020 [37], Morelli 2022 [39], Rachma 2025 [40]
		Carboplatin	None
		Oxaliplatin	None
Antimetabolites	Arterial vascular disease, venous thromboembolism, pericardial disease (cytarabine), coronary vasospasm (fluoropyrimidines)	5-Fluorouracil	None	Lexidrug Interactions Database [36], Herrmann 2020 [37], Morelli 2022 [39]
		Capecitabine	None
		Cytarabine	None
		Gemcitabine	None
		Methotrexate	None
		Pemetrexed	None
Anthracyclines	Cardiomyopathy, arrhythmias	Doxorubicin	None	Lexidrug Interactions Database [36], Balachandran 2024 [41], Cardinale 2015 [42], Herrmann 2020 [37], Li 2024 [43], Morelli 2022 [39]
		Daunorubicin	None
		Epirubicin	None
Antitumor antibiotics	Arterial vascular disease, pulmonary hypertension	Actinomycin D	None	Lexidrug Interactions Database [36], Balachandran 2024 [41], Herrmann 2020 [37]
		Bleomycin	None
		Mitomycin C	None
Topoisomerase inhibitors	Myocardial ischemia, hypotension	Irinotecan	None	Lexidrug Interactions Database [36], Balachandran 2024 [41], Pai 2000 [44]
		Topotecan	None
		Etoposide	None
Taxanes	Bradycardia, arrhythmia (QT prolongation, atrial fibrillation), arterial vascular disease, fluid retention	Docetaxel	None	Lexidrug Interactions Database [36], Chen 2017 [10], Herrmann 2020 [37], Morelli 2022 [39], Rowinsky 1991 [45]
		Paclitaxel	BP-lowering agent (Minoxidil) may increase hypotensive effect of hypotension-associated agent (Paclitaxel)
Vinca alkaloids	Arrhythmia, arterial vascular disease, myocardial ischemia	Vincristine	None	Lexidrug Interactions Database [36], Balachandran 2024 [41], Herrmann 2020 [37], Meinardi 2000 [46]
		Vinblastine	None
		Vinorelbine	None

BP, blood pressure; HTN, hypertension.

LDOM during Chemotherapy: Efficacy

Retrospective studies have consistently shown that LDOM improves hair regrowth and density following completion of chemotherapy [3–5]. One retrospective review investigating LDOM in BC patients diagnosed with pCIA and/or EIA included 100 patients, of whom 20 had pCIA alone, 69 had EIA alone, and 11 had combined pCIA and EIA [3]. Of the 31 patients who received chemotherapy, 30 received a taxane-based regimen and one received 5-fluorouracil, doxorubicin, and cyclophosphamide [3]. Among 37 patients with standardized clinical and trichoscopic photos available at baseline and follow-up, the authors found that combination therapy with LDOM and 5% topical minoxidil was superior to topical minoxidil alone for pCIA and EIA, showing improved treatment response (p = 0.002) and greater increases in hair density (p = 0.003) after mean treatment duration of 20.3 months (SD 17.9 months) [3]. However, this study did not investigate LDOM monotherapy compared to combination therapy with topical minoxidil or stratify its results by LDOM dose, representing important areas of future investigation [47]. They also did not stratify results by type of treatment-induced alopecia [3].

A second retrospective review investigated LDOM in 216 female BC patients with pCIA and/or EIA [4]. Thirty-one patients had pCIA, and 120 patients had both pCIA and EIA [4]. Chemotherapy regimens included doxorubicin, cyclophosphamide, and paclitaxel (n = 75); cyclophosphamide, methotrexate, and fluorouracil (n = 19); docetaxel, carboplatin, trastuzumab, and pertuzumab (n = 4); carboplatin and doxorubicin (n = 10); carboplatin and docetaxel (n = 4); docetaxel and cyclophosphamide (n = 5); and other regimens containing various combinations of paclitaxel, docetaxel, everolimus, capecitabine, gemcitabine, cyclophosphamide, methotrexate, fluorouracil, irinotecan, cisplatin, carboplatin, doxorubicin, epirubicin, vincristine, etoposide, cytarabine, or busulfan (n = 34) [4]. In this study, LDOM therapy led to significant improvements in hair shaft density at both the frontal (p = 0.008) and occipital (p = 0.004) scalp in 42 patients with quantitative trichoscopy assessments obtained at baseline and at follow-up after a median of 91 days (IQR 126 days) of treatment [4].

Finally, a third retrospective review of 51 BC patients receiving LDOM for various forms of alopecia (CIA, EIA, and other nonscarring and scarring alopecias) included 25 patients who received chemotherapy, although specific regimens were not specified [5]. Among these 25 BC patients, who received 39 unique LDOM regimens over a median treatment duration of 7.59 months (range 0.20–57.5 months), all achieved either stabilization or improvement of hair loss within 3–6 months of starting LDOM [5]. Collectively, the findings of these three retrospective reviews support the efficacy of LDOM in improving hair regrowth after chemotherapy treatment.

The administration of LDOM during chemotherapy may seem ill-advised as it would increase blood flow to the scalp, whereas SC, the predominant preventative intervention for CIA, decreases blood flow to limit exposure of the hair follicle to the chemotherapeutics [16, 20, 21]. This raises the concern that LDOM taken during chemotherapy might exacerbate alopecia due to increased delivery of chemotherapeutic agents to the hair follicle. However, a preclinical study suggests that LDOM may, in fact, have some protective effect against CIA. In this study, rats received minoxidil either topically (0.1 mL of 2% solution applied over 1 cm² of skin on the back) or via subcutaneous injection (0.1 mL of 2 mg/mL solution prepared by dissolving 10 mg tablets in sterile water) [6]. One hour after minoxidil administration, the rats received the chemotherapy agents cyclophosphamide or cytarabine; this process was repeated over six consecutive days [6]. All the rats who received subcutaneous minoxidil before cytarabine infusion (100%) demonstrated local protection against alopecia around the site of injection [6]. However, none of the rats who received topical minoxidil before cytarabine and none of the rats receiving cyclophosphamide, regardless of minoxidil mode of administration, exhibited any protection against alopecia [6]. Cyclophosphamide, an alkylating agent, belongs to a chemotherapy class with a higher incidence of CIA than cytarabine, an antimetabolite [12]. The lesser impact of cytarabine on the hair follicle may contribute to the ability of subcutaneous minoxidil to protect against alopecia in this group but not in the cyclophosphamide group.

A second animal study investigated the effects of systemic minoxidil administration (25 or 50 mg/kg) 1 h before paclitaxel injection over 7 days in previously epilated female mice [10]. The authors found that the minoxidil-treated mice exhibited hair regrowth after 13 days, whereas the untreated mice showed no regrowth [10]. Visual scoring of hair length and growth after 19 days revealed significantly greater improvements in the minoxidil group compared to the control group [10]. However, the minoxidil doses in this study far exceed those used in humans, likely resulting in residual active drug levels persisting after paclitaxel clearance. This limits the interpretation of any effects exerted by minoxidil specifically during active chemotherapy. Concurrent administration likely resulted in minoxidil already being present in circulation as paclitaxel levels declined, potentially enabling immediate support of follicular recovery at the earliest opportunity.

While no human studies have investigated systemic minoxidil during chemotherapy, topical minoxidil has been studied during chemotherapy. A small RCT investigated 2% topical minoxidil in 22 women with BC undergoing adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without methotrexate and vinblastine [7]. This study, in which topical minoxidil was applied twice daily throughout chemotherapy and for up to 4 months post-chemotherapy, found that the topical minoxidil group (n = 11) experienced a significantly shorter time from maximal hair loss to the first signs of regrowth than the control group (n = 9) (mean 86.7 days and mean 136.9 days, respectively; p = 0.03) [7]. However, two additional trials investigating 2% topical minoxidil twice daily throughout chemotherapy found no protective effect against CIA or shortening of time to hair regrowth [8, 9]. In one RCT, 48 female patients with various solid tumors, including BC (n = 41), soft tissue sarcomas (n = 5), and endometrial carcinoma (n = 2), receiving doxorubicin-containing chemotherapy, applied 5 mL of minoxidil 2% solution or placebo twice daily throughout chemotherapy until severe hair loss or limiting toxicity [8]. Most patients in both the minoxidil and placebo groups developed Grade 3 alopecia, defined as hair loss requiring the use of a wig before chemotherapy completion (88% and 92%, respectively; p > 0.05) [8]. The second study, which investigated topical minoxidil 2% twice daily starting 2 weeks prior to chemotherapy initiation and continuing throughout treatment, enrolled 10 patients, although only six complied with the study protocol and were evaluable [9]. Topical minoxidil was only applied to the area of the scalp superior and posterior to the right ear and compared to the area of the scalp superior and posterior to the left ear, not treated with topical minoxidil [9]. The 6 evaluable patients had cervical (n = 1), ovarian (n = 1), or endometrial (n = 4) cancers and received two chemotherapy regimens: cyclophosphamide, doxorubicin, and cisplatin (n = 5) or vincristine, mitomycin C, and cisplatin (n = 1) [9]. There was no difference in observed hair loss between the minoxidil-treated scalp and the non-treated scalp [9]. One patient with cervical cancer who received vincristine, mitomycin C, and cisplatin did not develop hair loss in either minoxidil or non-treated areas of the scalp [9]. None of these RCTs commented on the cancer outcomes in those using topical minoxidil [7–9]. Despite this, all three studies reported good overall tolerability of topical minoxidil, with no apparent toxicity in patients receiving chemotherapy [7–9].

These RCTs all used 2% topical minoxidil, which is less effective in promoting hair growth and density compared to 5% topical minoxidil or LDOM. An RCT comparing 2% versus 5% topical minoxidil in men with androgenetic alopecia (AGA) found significantly greater improvements in non-vellus hair count, patient rating of scalp coverage, and investigator rating of scalp coverage with the higher concentration [48]. Other RCTs comparing LDOM 1 mg daily with 5% topical minoxidil (once daily in women and twice daily in men) in AGA showed no significant difference in hair density improvement [49, 50]. Similarly, an RCT comparing LDOM 5 mg daily with 5% topical minoxidil twice daily in men with AGA also found no significant difference in terminal hair density on the frontal and vertex scalp between groups [51]. A retrospective review demonstrated that combining topical minoxidil with LDOM did not yield superior results in hair density or diameter compared to LDOM monotherapy in nonscarring alopecia [52]. Since CIA exhibits a histological pattern of nonscarring alopecia, adding topical minoxidil to LDOM may similarly offer no additional benefit over LDOM alone [53–55]^.

However, one of the RCTs examining topical minoxidil use during chemotherapy highlighted poor adherence to application protocols as a significant limitation [9]. The split-scalp trial investigating topical minoxidil 2% twice daily in 10 patients, in which 4 patients (40%) were unevaluable due to protocol nonadherence, reported that these patients had difficulty remembering to apply the minoxidil twice daily as prescribed [9]. The inconvenience of applying topical minoxidil often limits patient adherence and, therefore, benefits [52]. Additionally, topical minoxidil application introduces greater potential for variation in dosing as efficacy may depend on factors such as the amount applied and the specific areas of application. In contrast, LDOM may improve adherence by eliminating the need for burdensome topical application or the potential for skin irritation [52]. By providing standardized dosing in oral form, LDOM may also reduce variability in drug delivery, ensuring consistent systemic absorption without reliance on patient-dependent application techniques.

These studies suggest that starting LDOM during chemotherapy may decrease the time to hair regrowth, possibly by ensuring the drug is active as soon as chemotherapy clears. This approach may be more effective than waiting until after a washout period, which could lead to overestimating recovery time. Administering LDOM during chemotherapy might also lead to earlier improvements in hair density, as seen in studies of post-treatment use. However, it remains unclear if initiating LDOM during chemotherapy provides additional regrowth benefits compared to starting immediately after treatment ends. Although there is little evidence to suggest a protective effect of LDOM against CIA, even a small benefit could be valuable for patients receiving chemotherapeutics for which SC is less effective, such as anthracyclines [19].

Conclusions

This review establishes the theoretical groundwork and rationale for investigating LDOM during chemotherapy. Current evidence and mechanistic understanding suggest that LDOM may be safe to use during chemotherapy based on its favorable safety profile in retrospective studies of cancer patients and the routine use of other vasodilatory medications for BP management during cancer treatment [3–5, 28]. Preclinical studies showing a potential protective effect of subcutaneous minoxidil against cytarabine-induced alopecia and faster regrowth after systemic minoxidil was given concurrently with paclitaxel, respectively, provide support for further investigation of systemic minoxidil during chemotherapy treatment; however, the high dose used in the paclitaxel model limits direct translational relevance [6, 10]. Studies on topical minoxidil application during chemotherapy have demonstrated variable results for hair regrowth acceleration, though poor adherence and variations in application technique may have limited potential benefits [7–9]. LDOM could offer similar benefits with better adherence.

Clinical implementation of LDOM during chemotherapy requires careful consideration of this current evidence and its limitations. The lack of direct human studies evaluating LDOM safety and efficacy during active chemotherapy limits definitive recommendations regarding its use in this population. Initiation of LDOM during chemotherapy should be considered on an individualized basis for patients who desire intervention to mitigate CIA and in collaboration with the patient’s oncology and cardiology teams, particularly for patients with cardiac comorbidities or receiving potentially cardiotoxic chemotherapeutic agents [56]. Such decisions should also incorporate careful assessment of potential drug interactions. LDOM should be initiated at lower doses (e.g., 0.625–1.25 mg) to establish tolerability prior to up-titration, and patients should be monitored for cardiovascular AEs [56]. This individualized approach balances the promising safety profile of LDOM with appropriate clinical caution.

These mechanistic, preclinical, and clinical studies support further investigation of LDOM as a potential intervention during chemotherapy for CIA, particularly in patients receiving treatment regimens for which SC is less effective. Pilot case series or retrospective studies on patients already taking LDOM who continued during chemotherapy could provide initial insights into tolerability and potential benefits. If promising, larger prospective interventional studies are needed to provide high-quality evidence regarding safety and efficacy. These studies should incorporate objective measurements such as standardized global photography and trichoscopy, patient-reported outcomes assessing tolerability and quality of life, and comprehensive safety monitoring with particular focus on cardiovascular AEs, including pericardial effusion, and potential interactions with chemotherapeutic agents. Comparing LDOM regimens initiated during versus immediately after chemotherapy completion may clarify whether earlier initiation further shortens the duration of alopecia. Additional pilot studies should explore the use of LDOM in patients who are not expected to experience complete hair loss, such as investigating its concurrent use with SC to assess potential antagonistic or synergistic effects. Given the significant psychological impact and the lack of efficacious treatments for CIA, there is a need for further research investigating LDOM when initiated during chemotherapy.

Conflict of Interest Statement

Dr. Lacouture is an investigator for Hoth Therapeutics, consultant for Hoth Therapeutics and Marengo Therapeutics, and president of the Oncodermatology Society. Dr. Lo Sicco has been an investigator for Pfizer and Regen Lab, is a consultant for Pfizer, Lilly, Priovant, Veradermics, Ro, and Acquis, and is a board member of the Scarring Alopecia Foundation and American Hair Research Society. Dr. Markova is an investigator for Novartis, Novocure, Amryt Pharma, Incyte Corporation, Janssen, Kintara Therapeutics, grant recipient from the National Institute of Health, and consultant for ADH Therapeutics, Alira Health, AstraZeneca, Blueprint Medicines, Janssen, OnQuality, Protagonist Therapeutics, Sanofi, and Treeline Biosciences. Dr. Shapiro is an investigator for Pfizer and consultant for Pfizer, Lilly, Replicel Life Science, Regen Lab, Thirty Madison, DS Laboratories, and Almirall. Dr. Freites-Martinez is a speaker/faculty educator for ISDIN, an investigator for L’Oréal France, and a consultant for SHB law firm and Sanofi. Dr. Gordon, Dr. Tattersall, and author Kearney have no conflicts of interest. Dr. Kristen I. Lo Sicco was a member of the journal’s editorial board at the time of submission.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Conceptualization: K.I.L., A.G., and A.M. Literature review and drafting of the manuscript: C.A.K. Critical revision of the manuscript: A.G., A.M., A.F.M., I.W.T., J.S., M.E.L., and K.I.L. Supervision: K.I.L.

Funding Statement

This study was not supported by any sponsor or funder.