Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.     

Everolimus as treatment for breast cancer patients with bone metastases only: results of the phase II RADAR study

Purpose

Everolimus has shown to stop formation and activity of osteoclasts. Breast cancer patients with bone metastases only are candidates for effective but low toxic treatment.

Patients and methods

We evaluated everolimus in a double-blind, placebo-controlled, phase II, randomized discontinuation study in breast cancer patients with HER2 negative breast cancer patients with bone metastases only. After being stable on 8 weeks of everolimus 10 mg/day, patients were randomized to everolimus-continuation or placebo. Primary outcome was time (from randomization) to progression (TTP). Seventy-six patients would have had to be randomized to show a hazard ration (HR) of 0.5 for everolimus-continuation.

Results

Eighty-nine patients were enrolled in 4 years. Thirty-nine patients with SD after 8 weeks on everolimus were randomized to everolimus-continuation or placebo. TTP in patients with everolimus-continuation was 37.0 (95 % CI 16.7–40.3) versus 12.6 weeks (95 % CI 7.1–17.9) with placebo [HR 0.554 (95 % CI 0.282–1.09) p = 0.0818], adjusted for endocrine therapy [HR 0.464 (95 % CI 0.226–0.954) p = 0.037]. TTP in everolimus responders (n = 6) was 86 weeks.

Conclusion

The RADAR study is mainly hypothesis generating. It suggests that everolimus has single-agent activity, and patients with bone metastases only may retrieve long-term benefit from everolimus if they do not progress within 8 weeks of treatment.     

Reducing chemotherapy use in clinically high-risk,genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective,randomised phase 3 West German Study Group (WSG) PlanB trial

Purpose

To determine whether BPE in preoperative breast MRI influences patients’ recurrence-free survival (RFS).

Methods

Between February 2010 and December 2011, 804 consecutive women with invasive breast cancer who had undergone preoperative breast MRI and curative cancer surgery were identified. BPE was visually graded by two reviewers. We determined the correlation between BPE grade and other clinicopathological variables, including age, adjuvant therapy, menopausal status, histologic grade, T stage, N stage, lymphovascular invasion, molecular subtype, surgical margin status, and mammographic density. A Cox proportional hazards model was used to analyze the effects of clinicopathological variables and radiological findings (BPE grade, mammographic density) on RFS.

Results

High BPE was associated with premenopausal status (Ps < 0.0001), higher mammographic density (Ps < 0.0001), progesterone receptor positivity (Ps = 0.039, 0.007, respectively), presence of lymphovascular invasion (Ps = 0.008, 0.001, respectively), and close surgical margin (Ps < 0.0001). Recurrences were observed in 75 patients after a mean follow-up period of 61.8 months (range 4–81 months). Non-minimal BPE grade (RFS hazard ratio = 3.086, P = 0.003 for reader 1; RFS hazard ratio = 2.221, P = 0.075 for reader 2) and T3 stage were associated with worse outcomes in postmenopausal women. In premenopausal women, non-minimal BPE grade by readers 1 and 2 did not affect the patients’ outcomes.

Conclusions

Increased BPE on preoperative breast MRI in postmenopausal women has potential as a predictor of poor RFS.

     

Radiochemotherapy combined with regional pelvic hyperthermia induces high response and resectability rates in patients with nonresectable cervical cancer > or =FIGO IIB "bulky"

PURPOSE: To evaluate preoperative radiochemotherapy combined with regional pelvic hyperthermia in patients with nonresectable cervical cancer >/= International Federation of Gynecology and Obstetrics (FIGO) IIB "bulky" in a Phase II study. METHODS AND MATERIALS: Thirty-two patients with nonresectable FIGO IIB-IVA cervical cancer confined to the pelvis were treated with radiochemotherapy (5 x 1.8 Gy/wk, 45-50.4 Gy; cisplatin, 40 mg/m2/wk) and weekly regional pelvic hyperthermia (SIGMA-60 applicator, system BSD-2000; BSD Medical Corp., Salt Lake City, UT). Responders underwent hysterectomy if possible, whereas patients still unresectable received definitive hyperthermic radiochemotherapy. Feasibility, toxicity, as well as response and resectability, local progression free- and overall survival rates, were evaluated. RESULTS: Thirty of 32 patients completed treatment. Grade III/IV toxicities (National Cancer Institute-Common Toxicity Criteria) were diarrhea (n = 5), weight loss >10 kg (n = 4), and nausea (n = 2). Twenty-four of 32 patients (75%) achieved a partial remission after 45-50 Gy, and 20 patients underwent hysterectomy (18 patients, R0; 8 patients pCR). Three-year overall survival was 60%, with moderate (13%) rates of severe late toxicity. R0-resected patients had a favorable chronic toxicity profile and an excellent prognosis (3-year survival rate: 93%). Response depended on thermal parameters (vaginal reference point), whereas response, R0-resection, and FIGO stage are significant prognostic factors for survival. CONCLUSION: Preoperative hyperthermic radiochemotherapy (45-50 Gy) induces high response rates and enables curative surgery in a high proportion of patients with nonresectable cervical cancer. Therefore, the use of hyperthermia in conjunction with standard chemo-/radiotherapy +/- surgery may allow for more effective tumor treatment while decreasing the risk of complications in patients with locally advanced cervical cancer.     

Kombination der Antimalariamittel Mepacrin und Chloroquin bei therapieresistentem kutanem Lupus erythematodes

Antimalarials represent the first line in treatment of cutaneous lupus erythematosus (LE). However, some patients show no improvement on monotherapy with chloroquine or hydroxychloroquine. A 30-year-old female patient had treatment-resistant cutaneous LE exhibiting features of both LE tumidus and subacute cutaneous LE. Previously, the patient had been unsuccessfully treated with chloroquine, hydroxychloroquine, dapsone, and azathioprine, each in combination with variable doses of prednisolone. However, the LE lesions increased during these therapeutic regimens. A combination of chloroquine and mepacrine therapy led to improvement and then total clearing after 4 months of treatment.