Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials.

PURPOSE: Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials. PATIENTS AND METHODS: In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non-small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were "not at all," "a little," "quite a bit," and "very much." Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated. RESULTS: Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported "very much" toxicity, under-reporting by physicians ranged from 13.0% to 50.0%. CONCLUSION: Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials.

Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial.

BACKGROUND: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis. OBJECTIVES: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis. METHODS: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics. RESULTS: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported. CONCLUSIONS: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.

Hair loss with levetiracetam in five patients with epilepsy.

PURPOSE: To report cases of hair loss with levetiracetam (LEV) in epilepsy patient and summarise their demographic and clinical features. METHOD: All patients reported attended the epilepsy outpatient clinic of the West China Hospital, Sichuan University. Demographic and clinical information was obtained from medical records and by interview. All the patients were under regular follow up. RESULTS: Five epilepsy patients (4 females and 1 male) are reported. All developed hair loss within two months of starting LEV treatment. Three had idiopathic epilepsy, two symptomatic epilepsy. Three patients received LEV monotherapy, two combination treatment. None decided to switch away from LEV to another drug after developing hair loss, although the dose of LEV was reduced in one patient. CONCLUSION: Hair loss may be a rare side effect of LEV treatment in patients with epilepsy. LEV-related hair loss appears reversible if the dose is reduced or treatment is stopped.

Safety and efficacy of bimatoprost solution 0.03% topical application in patients with chemotherapy-induced eyelash loss.

Few dermatologic conditions carry as much anxiety and emotional distress as hair loss resulting from a disease condition such as alopecia areata or as a result of cytotoxic drug treatment, e.g., after chemotherapy. Bimatoprost 0.03% solution is a Food and Drug Administration-approved prescription product indicated for the treatment of eyelash hypotrichosis. The product was investigated in a double-masked, randomized, and placebo-controlled study in patients who had significant eyelash loss or hypotrichosis as a result of chemotherapy. Once-daily treatment with bimatoprost ophthalmic solution 0.03% to the upper eyelid margin restored eyelash growth and prominence more quickly than the slower, natural course of recovery observed in the vehicle control subjects. The eyelash prominence measured using a validated Global Eyelash Assessment (GEA) scale demonstrated a statistically significant increase over placebo following 6 months of treatment. Efficacy was also demonstrated using a validated objective digital image analysis methodology to show significant increase in eyelash length, thickness/fullness, and darkness in these patients. Bimatoprost was found to be well tolerated over the 1-year treatment period.

Symptoms before, during, and 14 months after the beginning of treatment as perceived by patients with lymphoma.

PURPOSE/OBJECTIVES: To explore occurrence of symptoms and relationships between them as perceived by patients with lymphoma before, during, and 14 months after the beginning of treatment. RESEARCH APPROACH: Qualitative and longitudinal. SETTING: A major oncology center in the United Kingdom. PARTICIPANTS: 10 adult patients with lymphoma (3 women and 7 men) were recruited at treatment initiation. METHODOLOGIC APPROACH: Semistructured audiotaped interviews were conducted with participants in median 15 days, 4 months, and 14 months after diagnosis. Analysis of the verbatim transcripts was inspired by interpretive description, which is a grounded approach articulating patterns emerging in relation to clinical phenomena. MAIN RESEARCH VARIABLES: Symptoms. FINDINGS: Symptoms commonly reported by patients in this sample were lack of energy, lymphadenopathy, weight loss, itching, pain, sadness, night sweats, sleeping difficulties, and hair loss. Co-occurring prediagnosis symptoms seem to have led patients to seek medical attention; co-occurring symptoms during treatment seem to have a cumulatively distressing effect. Several of the symptoms were described as interrelated, with one symptom leading to one or more other symptoms. CONCLUSIONS: The data confirm a complex symptomatology in patients with lymphoma. In addition, the findings support that co-occurring symptoms may have a synergistic effect on patients' health outcomes and add new knowledge about relationships between symptoms from patients' perspectives. INTERPRETATION: Illustrating symptoms and interrelationships between symptoms using diagrams may be useful to support communication as well as in identifying targets for symptom management.

[Acquired effluvium of head hair: common conditions in women]. / Unter hundert pro Tag ist normal: Wenn Frauen Haare lassen.

Acquired disorders of hair growth in women may present clinically either as effluvium or alopecia. The relevant pathologies include androgenetic alopecia, postpartum effluvium, tinea capitis, trichotillomania and alopecia areata.

Towards dissecting the pathogenesis of retinoid-induced hair loss: all-trans retinoic acid induces premature hair follicle regression (catagen) by upregulation of transforming growth factor-beta2 in the dermal papilla.

Diffuse hair loss ranks among the most frequent and psychologically most distressing adverse effects of systemic therapy with retinoids, which severely limits their therapeutic use even where clinically desired. Since the underlying mechanisms of retinoid-induced effluvium are as yet unknown, we have investigated the influence of the prototypic retinoid all-trans retinoic acid (ATRA, tretinoin) on the growth of human scalp hair follicles (HF) in culture. HF in the anagen VI stage of the hair cycle were cultured in the presence of 10(-8) or 10(-10) M ATRA. Compared with controls, hair shaft elongation declined significantly already after 2 d in the ATRA-treated group, and approximately 80% of the ATRA-treated HF had prematurely entered catagen-like stage at day 6, compared with 30% in the control group. This corresponded to an upregulation of apoptotic and a downregulation of Ki67-positive cells in ATRA-treated HF. Since transforming growth factor (TGF)-beta has been implicated as a key inducer of catagen, we next studied whether ATRA treatment had any effect on follicular expression. TGF-beta2 immunoreactivity was detected in the outer root sheath of anagen VI scalp HF. In catagen follicles, TGF-beta2 was also expressed in the regressing epithelial strand. After 4 d of ATRA treatment, TGF-beta2 was significantly upregulated in anagen HF in the dermal papilla (DP) and the dermal sheath, 7, and TGF-beta neutralizing antibody partially abrogated at RA induced hair growth inhibition. Real-time PCR confirmed a significant upregulation of TGF-beta2 transcripts in ATRA-treated hair bulbs. This study is the first to provide direct evidence that ATRA can indeed induce a catagen-like stage in human HF and suggests that this occurs, at least in part, via upregulation of TGF-beta2 in the DP. Therefore, topical TGF-beta2/TGF-beta receptor II antagonists deserve to be explored for the prevention and management of retinoid-induced hair loss.

Shedding: how to manage a common cause of hair loss.

Although telogen effluvium, or shedding-the most common type of diffuse hair loss in both women and men-is usually self-limiting, the condition may become chronic if the trigger is not identified and corrected. The authors discuss the physiologic and emotional triggers, clinical presentation, diagnosis, and management strategies, including the importance of patient education and reassurance.

The control of hair growth.

The hair follicle is one of a few human tissues containing stem cells. The stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge. From this reservoir stem cells migrate to hair matrix and start to divide and differentiate. Their behavior is controlled by numerous cytokines produced by cells of the dermal papilla. Dermal papilla cells and some cells of the inner and outer sheaths of the follicle from androgen-dependent hairs have androgen receptors in their cytoplasm and nucleus. Androgens indirectly control hair growth by influencing the synthesis and release of cytokines from the dermal papilla cells. Drugs affecting hair growth belong to one of the following groups: cytotoxic drugs, antiandrogens and drugs acting on potassium channels. Further development of drugs selective for certain steps in the process of hair growth will enable more successful therapy of hair growth disorders.

[Dermatologic complications of oral hormonal contraception (Gravistat)]. / Dermatologiczne powiklania doustnej antykoncepcji hormonalnej (Gravistat).

PIP: The author observed 120 women using the contraceptive preparation Gravistat over a 2-year period. The aim of this research was to establish which dermatological side effects occurred and the frequency with which they occurred in women taking Gravistat. Overall, only 8 women (6.7%) developed any side effects; the most frequent was uterine chloasma in 5 women (4.2%). Excessive hair loss occurred in 2 women (1.7%) and generalized itching in 1 case (0.8%). There were no other dermatological complications of a more serious nature. Therefore, the contraceptive effectiveness of Gravistat was considered to be 100%. (author's modified)^ieng