Significant Treatment-related Side Effects Research Articles

A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial

BackgroundAlthough survival rates for newly diagnosed prostate cancer patients are very high, most of them will likely suffer significant treatment-related side effects, depression, or anxiety, affecting their quality of life. ObjectiveThe aim of this study was to examine the effects of a 6-mo online home-based physical, mental, and social support intervention, the Prostate Cancer Patient Empowerment Program (PC-PEP), on preventing psychological distress among men undergoing curative prostate cancer treatment. Design, setting, and participantsIn a crossover randomized clinical trial of 128 men aged 50–82 yr scheduled for curative prostate cancer surgery or radiotherapy (± hormone treatment), 66 received the 6-mo PC-PEP intervention and 62 were randomized to a waitlist-control arm and received the standard of care for 6 mo, and then PC-PEP to the end of the year. The PC-PEP intervention consisted of daily e-mails with video instructions providing education, patient activation, and empowerment on healthy living including physical and mental health, dietary recommendations, social support, physical and pelvic floor fitness, stress reduction using a biofeedback device, social connection and intimacy, and social support. Outcome measurements and statistical analysisThe primary outcome was nonspecific psychological distress (clinical cutoff ≥20) measured at baseline, and at 6 and 12 mo using the Kessler Psychological Distress Scale (K10). Results and limitationsAt 6 mo, patients in the waitlist-control group had 3.59 (95% confidence interval: 1.12–11.51) times higher odds for nonspecific psychological distress and need for psychological treatment than men who received the PC-PEP intervention. At 12 mo, the wait-list control group that received the intervention at 6 mo had higher psychological distress than the early group. ConclusionsPC-PEP delivered early following diagnosis significantly prevented the burden of psychological distress in men undergoing curative prostate cancer treatment compared with standard of care, or late (6 mo later) intervention. Patient summaryIn this report, we looked at the effectiveness of a program (Prostate Cancer Patient Empowerment Program: PC-PEP) developed with patients' engagement on the mental distress of patients awaiting curative treatment for their prostate cancer. The PC-PEP program lasted for 6 mo, and it prescribed, described, and demonstrated daily aerobic and strength training, kegels (pelvic floor training to help with urinary and sexual function), dietary changes that have been shown to be helpful in the prevention of prostate cancer and prostate cancer progression, stress reduction using a biofeedback device, as well as social and emotional support. All patients in the PC-PEP program were invited to a monthly video conference with the leads of the program who appeared in the 6 mo of daily videos prescribing the activities the patients were asked to watch and follow. The leads were a prostate cancer oncologist and a scientist in prostate cancer quality of life research. Half of the patients in this study received PC-PEP daily for the first 6 mo and were re-assessed at the end of the year. The other half received standard of care for 6 month and then received the intervention to the end of the year. The results of the study show that, at 6 mo, this intervention was effective at reducing the mental distress that accompanies a prostate cancer diagnosis and treatment compared with the standard of care. Mental distress was significantly reduced when the intervention was received early, compared with that received late (6 mo after scheduled curative treatment). We conclude that multi-faceted patient education and empowerment programming of this kind that is developed with patient engagement from the start is crucial to the care of patients diagnosed with prostate cancer and should be implemented in the standard of care. While treatment for prostate cancer is highly successful, side effects that accompany most treatments significantly affect the quality of life of patients. Here, we describe PC-PEP, a patient education and activation program that is cost effective, highly enforced by patients, and successful at reducing the impact of prostate cancer active treatment–related side effects on their psychological state. To learn more about this project, please visit www.pcpep.org. The program is now being tested in a phase 4 implementation trial throughout Canada and internationally (New Zealand), and is being expanded and tested for other types of cancer.

El compromiso articular temporomandibular como causa de cefaleas agudas y crónicas y otros síntomas otoneurológicos

ObjectivesThe aim of this work is to introduce a new condition within temporomandibular disorders, temporomandibular joint compromise (TMJC), a mandibular movement limiting disorder of extra-articular traumatic cause, and evaluate the response rate and safety of treatment. The limiting cause of mandibular movement is the lack of space between the mandibular ramus and maxilla. The main symptoms of TMJC include headache, dizziness, and tinnitus. In many cases, the headache is previously diagnosed as a migraine. MethodsData were collected from 54 patients aged between 6 and 59 years that had a confirmed diagnosis of migraine according to the 3rd Edition of the International Headache Classification of the International Headache Society of 2018, and were treated for TMJC in a dental clinic. They also presented with other otolaryngological symptoms. A retrospective quasi-experimental study without a control group was carried out due to ethical considerations related to the harmless nature of the treatment. ResultsAfter treatment of TMJC, migraine symptoms disappeared in 52 patients (96.3%, P<.001), and persisted, although with clinical improvement, in 2 (3.7%). There was also an improvement in the other associated symptoms: dizziness disappeared in 23 out of 27 affected patients (85.21%, P<.001), and tinnitus disappeared in the 31 affected patients (100%, P<.001). No significant treatment-related side effects were observed. ConclusionsThis study shows the high rate of response and safety of the treatment of TMJC.

Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer

Patients with squamous cell carcinoma of the oropharynx are generally treated with (chemo) radiation. Patients with oropharyngeal cancer have better survival than patients with squamous cell carcinoma of other head and neck subsites, especially when related to human papillomavirus. However, radiotherapy results in a substantial percentage of survivors suffering from significant treatment-related side-effects. Late radiation-induced side-effects are mostly irreversible and may even be progressive, and particularly xerostomia and dysphagia affect health-related quality of life. As the risk of radiation-induced side-effects highly depends on dose to healthy normal tissues, prevention of radiation-induced xerostomia and dysphagia and subsequent improvement of health-relatedquality of life can be obtained by applying proton therapy, which offers the opportunity to reduce the dose to both the salivary glands and anatomic structures involved in swallowing.This review describes the results of the first cohort studies demonstrating that proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible. Also, the model-based approach for selecting patients for proton therapy in the Netherlands is described in this review and future perspectives are discussed.

Effect of exercise during adjuvant chemotherapy for breast cancer.

6524 Background: In 2018, an estimated 266,120 women faced the challenge of living with breast cancer and approximately 40,920 died from their disease. Nearly 100% of these women experienced significant treatment related side effects that negatively impact quality of life (QOL). Exercise has repeatedly demonstrated to alleviate many of the side effects, improve QOL, and decrease cancer recurrence and mortality. In spite of this evidence, women do not maintain exercise during treatment for breast cancer. The purpose of this randomized controlled trial was to determine the effectiveness of exercising the day chemotherapy is administered on 1) the persistence with an exercise program, 2) side effects, and 3) QOL. Methods: Eligible women were randomly assigned to a control or experimental group. As part of their treatment plan, all participants were referred to one of 14 community-based exercise centers to exercise. Experimental group also exercised at one of two cancer centers each day chemotherapy was administered. Outcome measures include exercise retention and chemotherapy, completion; cancer-related fatigue, nausea/vomiting, peripheral neuropathy, weight gain, and QOL. Outcome measures were assessed prior to every second course of chemotherapy and 3- and 6-months post-chemotherapy. Results: 273 women with Stage I-III breast cancer receiving chemotherapy were enrolled in the study. The number of participants who withdrew from exercise was higher among those in the control group (n= 16; 12.4%) compared with those in the experimental group (n = 10; 6.9%). At cycle 5, those in the experimental group reported less motor peripheral neuropathy than those in the control group (p = .018) and higher physical well-being scores than those in the control group (p = .047). Conclusions: The highest impact of the intervention was on attrition from exercise. Since participants in both the control and experimental groups exercised throughout chemotherapy, it is not surprising that the groups performed comparably with regard to side effects and QOL. Given the positive effects exercise has demonstrated on persons receiving cancer treatment in numerous studies, having patients exercise in the cancer center on the day of chemotherapy is a significant step toward engaging persons receiving chemotherapy in an exercise program.

IMPS-35UNUSUAL TUMOR INFILTRATING LYMPHOCYTES IN DE NOVO GLIOBLASTOMA FOLLOWING PRE-TREATMENT WITH ANTI-PD-L1 THERAPY FOR PRECEDING METASTATIC NSCLC: CASE PRESENTATION WITH DISCUSSION

The use of immunotherapy, specifically immune checkpoint inhibitors, is a rapidly emerging and evolving treatment modality for many solid tumor types. In this abstract, we describe a case of a 70 year old male with history of PD-L1 expressing metastatic poorly differentiated NSCLC treated with anti-PD-L1 therapy who was subsequently diagnosed with a glioblastoma with evidence of unexpected tumor infiltrating lymphocytes (TILs). The lung cancer was initially treated with combination chemotherapy with excellent response. This regimen was stopped prematurely due to significant treatment-related side effects. He then received the investigational anti-PD-L1 monoclonal antibody, MPDL3280A (Roche), under the Phase II Trial of MPDL3280A for PD-L1 positive locally advanced or metastatic NSCLC (NCT02031458). He experienced partial response without significant treatment-related side effects. Two weeks after completion of his 9th cycle of the study drug, he experienced altered mental status, personality changes, and confusion. A contrast brain MRI demonstrated a multifocal, rim-enhancing, left frontal lobe lesion with corpus callosal involvement. Of note, CT brain imaging prior to anti-PD-L1 study enrollment showed no evidence of abnormal enhancement. Stereotactic biopsy was performed with pathology showing glioblastoma with significant reactive lymphoid component noted (majority of lymphoid cells CD20 positive, scattered lymphocytes CD3 positive). He then underwent near image complete resection with pathology again demonstrating glioblastoma with 20-70% tumor necrosis, with 3 genomic alterations (CDKN2A/B loss; APCI1307K; TERT promoter – 124C > T) identified on Foundation One (Cambridge, MA) Next Generation Sequencing. This is the first reported case of a patient treated with anti-PD-L1 therapy for a high grade malignancy, who then developed a de novo glioblastoma with unusual biopsy findings of CD20 and CD3 positive TILs. Although more correlative studies are currently being performed, the immune implications for the use of immunotherapy for pre-treatment of glioblastomas may correspond to improved treatment response and patient outcomes.

The efficacy and toxicity of gemcitabine and cisplatin chemotherapy in advanced/metastatic bladder urothelial carcinoma

ObjectiveMany new agents have been introduced as an alternative to standard MVAC therapy with improved efficacy and lower toxicity profile in advanced bladder carcinoma. The aim of this study is to evaluate the response rate and toxic side effects of gemcitabine–cisplatin (GC) in patients with advanced/metastatic bladder carcinoma. MethodsBetween January 2001 and April 2006, 58 patients with histologically confirmed advanced/metastatic transitional cell carcinoma (TCC) were enrolled in the study. All patients received 1000mg/m2 gemcitabine administered via intravenous infusion of 30–60min on days 1, 8 and 15, and 70mg/m2 cisplatin as an infusion of 60-min on day 2. All toxicities were graded using the WHO scale and the National Cancer Institute scale. ResultsThe average number of cycles was 4.1. Neutropenia and thrombocytopenia were clinically significant treatment-related side-effects. Hematologic toxicity included mainly grades 3 and 4 neutropenia in 56%, grades 3 and 4 thrombocytopenia in 59%, and grades 3 and 4 anemia in 33% of patients. There was only one death from neutropenic sepsis. Complete response and partial response were obtained in 13 (22.4%) and 17 (29.3%) of patients, respectively, 17 (29.3%) of patients were found to have stable disease, and progression was observed in 11 patients (18.9%). Median survival for the whole group was 14.7 months (2–67). ConclusionsGC therapy is an effective regimen owing to its high tumor response and long survival with a low incidence of toxicity in advanced or metastatic patients.

La eficacia y toxicidad de la quimioterapia con gemcitabina y cisplatino en el carcinoma urotelial de vejiga avanzado/metastásico

ObjectiveMany new agents have been introduced as an alternative to standard MVAC therapy with improved efficiacy and lower toxicity profile in advanced bladder carcinoma. The aim of this study is to evaluate the response rate and toxic side effects of gemcitabine-cisplatin (GC) in patients with advanced/metastatic bladder carcinoma. MethodsBetween January 2001 and April 2006, 58 patients with histologically confirmed advanced/metastatic transitional cell carcinoma (TCC) were enrolled in the study. All patients received 1,000mg/m2 gemcitabine administered via intravenous infusion of 30-60minutes on days 1, 8 and 15, and 70mg/m2 cisplatin as an infusion of 60-min on day 2. All toxicities were graded using the WHO scale and the National Cancer Institute scale. ResultsThe average number of cycles was 4.1. Neutropenia and thrombocytopenia were clinically significant treatment-related side-effects. Hematologic toxicity included mainly grade 3-4 neutropenia in 56%, grade 3-4 thrombocytopenia in 59%, and grade 3- 4 anemia in 33% of patients. There was only one death from neutropenic sepsis. Complete response and partial response were obtained in 13 (22.4%) and 17 (29.3%) of patients, respectively, 17 (29.3%) of patients were found to have stable disease, and progression was observed in 11 patients (18.9%). Median survival for the whole group was 14.7 months (2-67). ConclusionsGC therapy is an effective regimen owing to its high tumor response and long survival with a low incidence of toxicity in advanced or metastatic patients.

Prevention of Herpes Zoster Pain

SUMMARYHerpes zoster (HZ; shingles) is frequently accompanied by significant pain that may precede rash appearance and persist as postherpetic neuralgia (PHN). PHN results in detriment to quality of life and has healthcare cost implications. Treatment for PHN often provides poor relief, with up to half of patients achieving less than 50% reduction of pain and significant treatment-related side effects. Vaccination against varicella reduces the number of individuals in the population carrying latent wild virus who can develop HZ. Enhancing zoster-specific cell-mediated immunity of older adults by HZ vaccination has been shown to reduce the incidence of both HZ and PHN. Treatments applied during the acute phase of HZ that may reduce pain duration are discussed, including antiviral drugs, anti-inflammatory steroids, effective analgesia and nerve blocks.

Open-label add-on treatment trial of minocycline in fragile X syndrome

BackgroundFragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in fmr1 knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS.MethodsTwenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline) and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C) Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI), and the visual analog scale for behaviour (VAS). Side effects were assessed using an adverse events checklist, a complete blood count (CBC), hepatic and renal function tests, and antinuclear antibody screen (ANA), done at baseline and at 8 weeks.ResultsThe ABC-C Irritability Subscale scores showed significant improvement (p < 0.001), as did the VAS (p = 0.003) and the CGI (p < 0.001). The only significant treatment-related side effects were minor diarrhea (n = 3) and seroconversion to a positive ANA (n = 2).ConclusionsResults from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the fmr1 knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted.Trial registrationClinicalTrials.gov Open-Label Trial NCT00858689.

Effectiveness of Ketorolac Tromethamine in Prevention of Severe Retinopathy of Prematurity

This study assessed the effectiveness of the use of ketorolac tromethamine to reduce retinopathy of prematurity (ROP) incidence and its progression to more severe forms. Forty-seven preterm newborn infants with a birth weight (BW) of 1,000 grams or less and/or a gestational age (GA) of 29 weeks or less were enrolled in the study when avascular retina zone I or ROP any stage were diagnosed at screening. Studied infants were randomized to receive ketorolac tromethamine ophthalmic solution in one eye and a drop of placebo in the other eye, until ROP requiring treatment or full retinal vascularization was diagnosed. Only 2 newborn infants did not develop ROP. Among 45 newborn infants who developed ROP, 6 showed different ROP staging between the two eyes, 4 of which had a better outcome in the eye receiving ketorolac tromethamine. The differences between ROP stagings were not significant even when analyzed by GA and BW subgroups. No significant treatment-related side effects occurred. This report suggests that ketorolac tromethamine ophthalmic solution cannot reduce the risk of developing severe ROP in preterm infants.

Heterotopic ossification after total hip arthroplasty (THA) in congenital hip disease: comparison of two different prophylactic protocols

We aimed to evaluate retrospectively the efficacy of combined postoperative radiotherapy and indomethacin compared to indomethacin alone for the prevention of heterotopic ossification (HO) in high-risk patients with congenital disease of hip (CDH) undergoing total hip arthroplasty (THA). Fifty-five patients received indomethacin alone (Group A), while 44 patients received the combined protocol (Group B). Patients >or=55 years were enrolled in Group B and those younger than 55 years in Group A. Patients were evaluated radiologically for the presence of HO 6 months after the operation. The incidence of HO in Group A was 34.5% (95% confidence interval 22.2-48.6%), while the respective incidence in Group B patients was 27.3% (95% CI 15.0- 42.8%). The difference was not statistically significant (p=0.5). No significant treatment-related side effects were reported. This is the first study evaluating the impact of HO prophylaxis in an immiscible population of patients with secondary arthritis due to CDH undergoing THA. Further future randomised evidence is required in order to ascertain the observed trend towards improved efficacy of the combined protocol for HO development.

Open-Label Treatment Trial of Lithium to Target the Underlying Defect in Fragile X Syndrome

In fragile X syndrome (FXS), it is hypothesized that absence of the fragile X mental retardation protein (FMRP) disrupts regulation of group 1 metabotropic glutamate receptor (mGluR and mGluR5)-dependent translation in dendrites. Lithium reduces mGluR-activated translation and reverses phenotypes in the dfxr mutant fly and fmr1 knockout mouse. This pilot add-on trial was conducted to evaluate safety and efficacy of lithium in humans with FXS. Fifteen individuals with FXS, ages 6-23, received lithium titrated to levels of 0.8-1.2 mEq/L. The primary outcome measure, the Aberrant Behavior Checklist --Community Edition (ABC-C) Irritability Subscale, secondary outcome measures (other ABC-C subscales, clinical global improvement scale (CGI), visual analog scale for behavior (VAS), Vineland Adaptive Behavior Scale (VABS)), exploratory cognitive and psychophysiological measures and an extracellular signal-regulated kinase (ERK) activation assay were administered at baseline and 2 months of treatment. Side effects were quantified with a standardized checklist and lithium level, complete blood count (CBC), thyroid stimulating hormone (TSH), and chemistry screen were done at baseline, 2 weeks, 4 weeks and 2 months. The only significant treatment-related side effects were polyuria/polydipsia (n = 7) and elevated TSH (n = 4). Although the ABC-C Irritability Subscale showed only a trend toward improvement, there was significant improvement in the Total ABC-C score (p = 0.005), VAS (p = 0.003), CGI (p = 0.002), VABS Maladaptive Behavior Subscale (p = 0.007), and RBANS List Learning (p = 0.03) and an enhanced ERK activation rate (p = 0.007). Several exploratory tasks proved too difficult for lower-functioning FXS subjects. Results from this study are consistent with results in mouse and fly models of FXS, and suggest that lithium is well-tolerated and provides functional benefits in FXS, possibly by modifying the underlying neural defect. A placebo-controlled trial of lithium in FXS is warranted.

Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: Report of a prospective (Phase II) multicenter study

Background: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. Methods: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 ± 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. Results: Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 ± 0.68 ug/mL (median, 3.64 μg/mL; range, 1.31 to 14.39 μg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 ± 1.3 mm at 6 months versus 41.0 ± 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% ± 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 ± 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 ± 32.9 ng/mL at 3 months (not signifcant versus baseline) and to 66.4 ± 24.2 ng/mL at 6 months ( P = .022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline ( P < .05). Conclusion: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression. (J Vasc Surg 2002;36:1-12.)

Re-irradiation and external hyperthermia in locally advanced, radiation recurrent, hormone refractory prostate cancer: a preliminary report

The purpose of this report is to present the preliminary results of re-irradiation and external hyperthermia in patients with locally advanced, previously irradiated, hormone refractory prostate cancer. Three consecutive patients with symptomatic, locally advanced, previously irradiated and hormone refractory prostate cancer were treated with further irradiation (30.6-50 Gy) and external hyperthermia (5-8 treatments). All patients had complete resolution of symptoms lasting for 12-24 months. Significant tumour shrinkage, including complete tumour response, was demonstrated by CT and endoscopy. In one case, at 2 years after re-treatment, there is continued tumour regression and bone regeneration in the pelvis. Two patients had local control of tumour, which continued until most recent follow-up at 12 months and more than 24 months, respectively. Another case developed local recurrence at 17 months. At most recent follow-up, no patient has experienced significant treatment-related side effects. In these patients with no other therapeutic alternatives, re-irradiation and hyperthermia can provide durable tumour response for more than a year, resulting in significant improvement in quality of life. Further clinical studies are warranted.

Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies.

In order to establish a safe and reliable treatment for human immunodeficiency virus (HIV)-associated scabies, we have treated 60 episodes of scabies in this setting, occurring in 39 patients, with one of the following regimens: (i) topical treatment with benzyl benzoate solution; (ii) single-dose oral treatment with ivermectin alone; and (iii) combination therapy with benzyl benzoate solution and oral ivermectin, employing the same regimens as single-agent therapy. Patients were stratified according to the severity score of the disease and the outcome (eradication, relapse, failure). We found that both benzyl benzoate and ivermectin alone were quite effective in mild to moderate scabies, but they were both associated with an unacceptable rate of relapse and failure in severe or crusted scabies. In contrast, combined treatment produced an optimal rate of success, without significant treatment-related side-effects. Therefore, we consider that combination treatment with benzyl benzoate solution and oral ivermectin is preferable to single-agent therapy in crusted scabies occurring in HIV/acquired immune deficiency syndrome patients.