|Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial
Nangia J et al., JAMA. 2017 Feb 14;317(6):596-605.
PubMed ID: 28196254
Chemotherapy-induced alopecia is one of the most distressing adverse events in women undergoing cancer treatment. Scalp cooling is hypothesized to induce cutaneous vasoconstriction that reduces blood flow to hair follicles and subsequent uptake of chemotherapy.
A study by Nangia and colleagues explored the efficacy of a scalp cooling device in chemotherapy-induced alopecia among women with breast cancer on adjuvant/ neoadjuvant chemotherapy.
- Patients: women with stage 1-II breast cancer for adjuvant/neoadjuvant chemotherapy (at least 4 cycles of taxane and/or anthracycline-based chemotherapy)
- Study design: phase III open-label trial
- Experimental: Scalp cooling 30 mins. prior to, during and 90 mins. after chemotherapy
- Control: No scalp cooling
- Primary: hair preservation after 4th cycle of chemotherapy (CTCAE v4.0 alopecia grade 0 (no hair loss) or grade 1 (<50% hair loss not requiring a wig)
- Secondary: hair preservation after 4th chemotherapy cycle assessed by clinician and participant, use of wigs/head wraps, participant-reported comfort, QOL
- 182 patients randomized 2:1 to scalp cooling (n=119) vs. no scalp cooling (n=63)
- Baseline patient characteristics: mean age 52 yrs., 83% white, 65% taxane, 35% anthracycline, 61% stage II, 32% doxorubicin/cyclophosphamide, 32% docetaxel/cyclophosphamide, 91% fully active
Table 1: Efficacy Outcomes in Modified ITT Population
- Rates of hair preservation varied by study site and treatment received (taxane vs. anthracycline).
- QOL was not significantly different between cooling group with hair preservation, cooling group without hair preservation and noncooling group.
- Depression and anxiety scores were normal at baseline and after 4 cycles of chemotherapy in all treatment groups.
- Safety (only device-related adverse events)
- 54 adverse events reported in the cooling group; 46 anticipated, 8 unanticipated events
- No serious adverse events were reported.
- Most common adverse event was headache.
- All adverse events were grade 1-2: chills, dizziness, headache, nausea, paresthesia, pruritus, sinus pain, skin and subcutaneous tissue disorders, skin ulceration
- Unanticipated adverse events: dry skin, scalp pain
- Median rating on the comfort scale was reasonably comfortable
- Among women with early breast cancer who underwent adjuvant/neoadjuvant taxane or anthracycline-based chemotherapy, scalp cooling significantly increased hair preservation rate compared to the control group. After the 4th cycle of chemotherapy, patients were more likely to have less than 50% hair loss with scalp cooling.
- Scalp cooling did not appear to improve QOL compared to the control group. Study authors used selected items from several functioning scales to assess QOL related to alopecia for which there is no standardized metric. Anxiety and depression scores remained stable from baseline until the 4th cycle of chemotherapy.
- Adverse events related to the device were low grade and tolerable. Majority of the patients found the cooling cap to be reasonably comfortable.
- Differences in hair preservation rate was observed between study sites. Factors attributed to this finding include cap fitting technique, type of chemotherapy regimen, patient characteristics (e.g. ethnicity), interobserver variability, among others.
- Patients who received taxane-based chemotherapy had higher rates of hair preservation compared to those who had anthracycline-based regimens. This is consistent with previous literature.
- Scalp cooling appears to be an attractive option to reduce alopecia among women on adjuvant chemotherapy for early breast cancer. However, long-term toxicity remains a concern, particularly scalp metastases due to reduced chemotherapy uptake supposedly induced by scalp cooling. Furthermore, the effect of scalp cooling with prolonged treatment (more than 4 cycles of chemotherapy) needs to be assessed in the adjuvant setting as well as advanced disease. Data collection is currently ongoing; updated results are forthcoming and highly anticipate.
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Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
Fizazi K et al., N Engl J Med. 2017 Jul 27;377(4):352-360.
PubMed ID: 28578607
The addition of docetaxel to ADT has demonstrated improvement in survival in clinical trials (Lancet 2016; 387: 1163-77). Hence, it is current standard of care for metastatic castrate-sensitive prostate cancer. However, chemotherapy poses challenges in terms of safety and patient selection. Abiraterone acetate (prodrug of abiraterone) is an inhibitor of cytochrome P-450c17, involved in androgen synthesis. When given in combination with prednisone and ADT, abiraterone showed anti-tumor activity in men with high-risk, localized prostate cancer on neoadjuvant treatment (J ClinOncol 2014; 32: 3705-15).
Researchers conducted the LATITUDE trial to determine the efficacy of abiraterone with prednisone and ADT vs. ADT with placebos as first line treatment in metastatic, castration-sensitive prostate cancer.
- Patients: histologically confirmed metastatic castrate-sensitive prostate cancer without neuroendocrine differentiation or small-cell histologic features, with 2 out of 3 high-risk features (Gleason ≥8, at least 3 bone lesions, measurable visceral metastases), ECOG 0-2, no previous treatment for metastatic disease (except ≤ 3 mos. ADT)
- Study design: phase III double-bind, placebo-controlled RCT
- Experimental: Abiraterone 1,000 mg/day + Prednisone 5 mg/day
- Control: ADT + Placebos
- Primary: radiographic PFS, OS
- Secondary: time to next symptomatic skeletal event (SSE), TTP (PSA), time to next therapy for prostate Ca, time to initiation of chemotherapy, time to pain progression
- 1,199 patients randomized to abiraterone (n=597) and placebo (n=602)
- Baseline patient characteristics: median age 68 yrs., 98% Gleason ≥8, 50% baseline pain score 0-1, 98% ≥3 bone mets, 96% Gleason score ≥8 + ≥3 bone lesions, 98% bone disease, 83% hormonal therapy, 75% GnRH agonist/antagonist
Table 1: Efficacy Outcomes
- Subsequent therapy: 21% vs. 41% overall, mostly docetaxel (34% vs. 40%).
- Most common any grade adverse events with abiraterone: hypertension (37% vs. 22%), hypokalemia (20% vs. 4%), increased ALT (16% vs. 13%), back pain (18% vs. 20%)
Table 2: Adverse Event and Treatment Summary
- Grade 4 adverse events with abiraterone (≤ 1%): hypokalemia, increased ALT and AST, hyperglycemia, cardiac disorder, anemia
- Grade 4 adverse events with placebo (≤ 1%): hypertension, hypokalemia, anemia, spinal cord compression
- First line treatment with abiraterone in combination with ADT and prednisone significantly improved radiographic PFS and OS compared to ADT with placebo in newly diagnosed metastatic castrate-sensitive prostate cancer with at least two high-risk features. Abiraterone reduced the risk of disease progression or death by 53% and death by 38%, with a consistent advantage across all predefined subgroups.
- Secondary endpoints including time to progression of pain or PSA, time to symptomatic skeletal event, time to chemotherapy and time to next prostate cancer therapy all favoured the abiraterone group. Furthermore, significantly more patients on abiraterone achieved PSA response compared to placebo.
- Adverse events were consistent with previous literature; hypertension and hypokalemia were most commonly reported in the abiraterone arm. High grade adverse events, treatment interruption, dose reduction and discontinuation were more often reported in the abirateron arm, although rates of serious adverse events and treatment-related deaths did not significantly differ.
- Findings from the LATITUDE trial are comparable to results from the STAMPEDE trial that randomized men with newly diagnosed locally advanced or metastatic castrate-sensitive with high-risk features to docetaxel with hormonal treatment vs. hormonal therapy (Lancet 2016; 387: 1163-77). Docetaxel with hormonal therapy significantly improved OS (HR 0.68), FFS (HR 0.61) and prostate Ca-specific survival (HR 0.79).
- The addition of abiraterone to ADT and prednisone in newly-diagnosed metastatic high-risk castrate-sensitive prostate cancer significantly improved survival and delayed time to pain, PSA progression and chemotherapy compared to ADT. Although the safety profile is favourable compared to chemotherapy in cross trial comparisons, the cost of abiraterone is much higher taken continuously until progression than six finite cycles of docetaxel. Pharmacoeconomic models will need to be studied but will certainly favour abiraterone when it becomes generic.
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