An interim analysis of the SCALP trial, reported in JAMA by Julie Nangia, MD, of Baylor College of Medicine, and colleagues, showed that use of a scalp-cooling device significantly reduced hair loss in women receiving chemotherapy for stage I or II breast cancer compared with no scalp cooling.¹ The study was stopped early on the basis of efficacy. Updated data from this trial were presented at the 2017 ASCO Annual Meeting.² In the same issue of JAMA, Hope S. Rugo, MD, of the Helen Diller Family Comprehensive Cancer Center, and colleagues reported the results of a prospective cohort study showing that use of a scalp-cooling device reduced hair loss in women receiving nonanthracycline chemotherapy for early-stage breast cancer.³

SCALP Trial Details

In the SCALP study,^1,2 182 women from 7 U.S. sites who required chemotherapy were randomized 2:1 between December 2013 and September 2016 to receive scalp cooling (n = 119) or no scalp cooling (n = 63). All patients were planned to receive at least four cycles of taxane- and/or anthracycline-based chemotherapy for curative intent. Scalp cooling was performed using a cap scalp-cooling device for 30 minutes prior to, during, and for 90 minutes after each chemotherapy infusion.

Hope S. Rugo, MD

The primary efficacy endpoint was successful hair preservation assessed using the Common Terminology Criteria for Adverse Events version 4.0 scale, with preservation defined as grade 0 (no hair loss) or grade 1 alopecia (< 50% hair loss not requiring a wig) at the end of four cycles of chemotherapy. Outcome was assessed by a clinician unaware of treatment assignment. At the time of the preplanned interim analysis, 142 patients (95 in the cooling group and 47 in the control group) had completed 4 cycles of chemotherapy and were evaluable for the primary endpoint (modified intent-to-treat population).

For the cooling and control groups in the modified intent-to-treat population: median age was 53 and 55 years; 75% and 82% were white; all had grade 0 alopecia at baseline; the major chemotherapy type was anthracycline in 34% and 40% and taxane in 66% and 60%; and disease stage was I in 40% and II in 60% in both. The most common scheduled chemotherapy regimens were doxorubicin at 60 mg/m² plus cyclophosphamide at 600 mg/m² in 32% and 36%, docetaxel at 75 mg/m² plus cyclophosphamide at 600 mg/m² in 36% and 19%, and docetaxel at 75 mg/m² with carboplatin target AUC = 6 mg × min/mL and standard-dose trastuzumab (Herceptin) in 22% and 23%.

Hair Preservation Rates

At interim analysis, successful hair preservation was observed in 48 of 95 women in the cooling group (50.5%, 95% confidence interval [CI] = 40.7%–60.4%) vs 0 of 47 women in the control group (0%, 95% CI = 0%–7.6%), yielding a success rate difference of 50.5% (95% CI = 40.5%–60.6%, P < .001). Since the P value crossed the interim analysis superiority boundary (P = .0061), the data and safety monitoring board recommended study termination in September 2016. Hair preservation in the cooling group consisted of grade 0 alopecia in 5 patients (5.3%) and grade 1 alopecia in 43 patients (45.3%). Rates of hair retention were 53.1% vs 0% as assessed by patients and 55.8% vs 0% as assessed by oncologists.² Wigs or head wraps were used by 63% vs 100% of patients. 

Those who underwent scalp cooling were significantly more likely to have less than 50% hair loss after the fourth chemotherapy cycle….

— Julie Nangia, MD, and colleagues

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Differences in hair preservation rates in the cooling group were observed according to the study site and drug treatment. Hair preservation rates ranged from 0% at a site enrolling only 1 patient to 68.6% at a site enrolling 51 patients. Overall, success was reported in 7 of 32 patients (24%) receiving anthracycline-based treatment and in 41 of 63 patients (63%) receiving taxane-based treatment. In an exploratory post hoc analysis accounting for site effects, estimated rates of hair preservation were 16% with anthracycline-based treatment and 59% with taxane-based treatment.

Adverse Events

Adverse events were collected only for the cooling group. A total of 71 adverse events were reported in the final analysis, with all being grade 1 or 2. Adverse events included chills, dizziness, headache, nausea, paresthesia, pruritus, sinus pain, skin and subcutaneous tissue disorders, and skin ulceration. The most common events were headache, which occurred in 11.7%, 8.5%, 1.1%, and 4.8% during chemotherapy cycles 1 through 4, and nausea, which occurred in 4.4%, 1.7%, 1.1%, and 1.2% during cycles 1 through 4. Of the eight grade 2 adverse events, seven were headache and one was scalp pain. No serious adverse events were reported.

No statistically significant differences were observed between groups in changes from baseline in quality of life assessed by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30, Hospital Anxiety and Depression Scale, and summary scale of the Body Image Scale.

A final analysis of the trial including an additional 60 enrolled patients was presented at the 2017 ASCO Annual Meeting.²

The investigators concluded: “Among women with stage I to II breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have less than 50% hair loss after the fourth chemotherapy cycle compared with those who received no scalp cooling. Further research is needed to assess longer-term efficacy and adverse effects.”

Study in Women Not Receiving Anthracycline Treatment

In the second study,³ 101 evaluable patients from 5 U.S. centers with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens underwent scalp cooling with a cap device beginning 30 minutes prior to and continuing until 90 to 120 minutes after chemotherapy -administration. A concurrent age- and chemotherapy treatment–matched control group of 16 patients was included. The study was performed between August 2013 and October 2014.

The primary outcome measure was self-estimated hair loss using the Dean scale at 4 weeks after the last dose of chemotherapy, with a score of 0 to 2 (≤ 50% hair loss) being defined as treatment success. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later using five measures from the European Organisation for Research and Treatment of Cancer Breast Cancer–Specific Quality-of-Life Questionnaire.

Among all patients, the mean age was 53 years (range = 28–77 years) and 77.0% were white, 9.0% were black, and 10.7% were Asian. No patients in the scalp-cooling group received anthracyclines. The most common chemotherapy regimen was docetaxel and cyclophosphamide for four to six cycles (75%), with other regimens including docetaxel and carboplatin (12.8%), weekly paclitaxel (11.9%), and docetaxel (1%). The median duration of chemotherapy was 2.1 months.

Rates of Hair Loss

Hair loss of 50% or less was observed in 67 of 101 patients (66.3%, 95% CI = 56.2%–75.4%) vs 0 of 16 patients in the control group (P < .001). In the scalp-cooling group, maximum Dean score was 0 in 5.0% of patients, 1 (> 0% to ≤ 25% hair loss) in 30.7%, and 2 in 30.7%. A post hoc analysis by an independent panel performed before all patients had reached the 1-month evaluation indicated hair loss of 50% or less in 74 of 88 patients (84.1%) evaluated.

Quality of Life and Adverse Events

Patients in the scalp-cooling group had significantly better outcome on three of the five quality-of-life measures: 27.3% vs 56.3% reported feeling less physically attractive (P = .02); 32.4% vs 60.0% reported being quite or very upset by hair loss (P = .04); and 15.9% vs 37.5% reported being quite or very dissatisfied with their body (P = .04).

On the Patient Symptom Survey 0 to 100 (worst) scale, chilliness was reported by 98% of the scalp-cooling group, with a mean score of 49.5; headache was reported by 41%, with a mean pain level of 39.3; and scalp pain was reported by 71%, with a mean pain level of 24.2. Mild headache was reported as an adverse event in 3.8% of patients. Scalp cooling was discontinued in 2.8% of patients due to feeling cold.

The investigators concluded: “Among women undergoing nonanthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. Further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects.” ■

DISCLOSURE: The SCALP trial was supported by Paxman Coolers Ltd, which contracted with Baylor College of Medicine to conduct the study. The study reported by Rugo et al was funded by Dignitana AB, Lazlo Tauber Family Foundation, Anne Moore Breast Cancer Research Fund, and Friedman Family Foundation. For full disclosures of the studies’ authors, visit www.jama.jamanetwork.com.

REFERENCES

1. Nangia J, Wang T, Osborne C, et al: Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: The SCALP randomized clinical trial. JAMA 317:596-605, 2017.

2. Nangia J, Wang T, Osborne C, et al: Scalp Cooling Alopecia Prevention Trial (SCALP) for patients with early stage breast cancer. 2017 ASCO Annual Meeting. Abstract 10088. Presented June 3, 2017.

3. Rugo HS, Klein P, Melin SA, et al: Association between use of a scalp cooling device and alopecia after chemotherapy for breast cancer. JAMA 317:606-614, 2017.