Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study).

OBJECTIVE: Azacitidine (Vidaza® ) is the standard treatment for patients with higher-risk myelodysplastic syndromes (MDS) not eligible for allogeneic stem cell transplantation. In the noninterventional study PIAZA, we evaluated the effectiveness and safety of azacitidine treatment in 149 patients with higher-risk MDS, chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) in routine clinical practice. METHOD: Patients were treated according to physician's discretion. Besides evaluation of safety and effectiveness, impact of covariates on progression-free survival (PFS) was assessed. RESULTS: Median age of patients was 75 years. 61.1% of patients were diagnosed with MDS, 31.5% with AML and 7.4% with CMML. Patients were treated with azacitidine for a median of seven cycles. Median PFS was 10.9 months. Median OS was 14.1 months. Two-year survival rate was 28.9%. 45.9% of patients showed CR or PR. Stable and progressive disease were observed in 37.2% and 8% of patients, respectively. Transfusion independence was reported in 64 of 89 patients. Eastern cooperative oncology group (ECOG) performance status (PS) and red blood cell (RBC) transfusion before azacitidine therapy were identified as predictive factors for PFS. CONCLUSION: In conclusion, we estimated the duration of PFS in a real-world setting and identified ECOG PS and RBC transfusion as predictive factors for PFS. The safety of azacitidine showed a similar profile as demonstrated in the pivotal clinical trials.

AIO LQ-0110: a randomized phase II trial comparing oral doxycycline versus local administration of erythromycin as preemptive treatment strategies of panitumumab-mediated skin toxicity in patients with metastatic colorectal cancer.

BACKGROUND: Dermatologic toxicities, especially akne-like skin rash, are the most common side-effects associated with anti-epidermal growth factor receptor (EGFR) therapy. Preemptive treatment with oral tetracyclines is recommended as a standard. Topical prophylactic options have thus far not been compared to tetracyclines. In the current study, we sought to establish an alternative topical treatment. PATIENTS AND METHODS: In this multicentre, randomized, open-label phase II study patients with (K)Ras-wildtype colorectal cancer receiving panitumumab were randomized (1:1) to receive either doxycycline 100 mg b.i.d. (standard arm) or erythromycin ointment 2% followed by doxycycline in case of insufficient activity. The primary endpoint was the percentage of patients developing no skin toxicity ≥ grade 2 at any time during the first 8 weeks of panitumumab treatment. Skin toxicity was assessed using the NCI CTCAE v 4.0. Secondary endpoints comprised the assessment of skin toxicity using a more thorough grading system (WoMo score), evaluation of skin-related (DLQI) and global quality of life (EORTC QLQ C30). RESULTS: In total, 88 patients were included in this trial. 69% of the patients in the erythromycin arm suffered from skin toxicity of grade ≥ 2 versus 63% in the standard arm (P = n.s.). However, as per WoMo score significantly more patients in the erythromycin arm developed moderate or severe skin toxicity at earlier time points. Skin related and overall quality of life was comparable between both arms. CONCLUSIONS: Based on this data erythromycin cannot be regarded as an alternative to doxycycline as prevention of EGFR-related skin toxicity.

Neoadjuvant Chemotherapy with Docetaxel, Carboplatin and Weekly Trastuzumab Is Active in HER2-Positive Early Breast Cancer: Results after a Median Follow-Up of over 4 Years.

INTRODUCTION: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years. Here we present 4-year follow-up data for a cohort of 78 patients treated with neoadjuvant TCH. METHODS: Between 2009 and 2014 we treated 78 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) every 3 weeks (q3w) and trastuzumab (4 mg/kg loading dose then 2 mg/kg) q1w. Lymph node involvement was verified by sentinel lymph node or core-cut biopsy. Patients were diagnosed at a mean age of 55.5 years; 65.4% had hormone receptor-positive tumors, 34.6% presented with grade 3 disease and 51.3% of patients were node positive. Patients were monitored every 2 cycles by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery, trastuzumab was continued q3w up to 1 year. RESULTS: No grade III/IV toxicities occurred and no case of congestive heart failure was observed. Neither dose modifications nor dose delays were necessary. 34 of the 78 patients (43.6%) achieved a pCR, 27 of the 40 node-positive patients (67.5%) experienced nodal conversion. After a median follow up of 48.5 months the disease-free survival (DFS) was 84.6%, the distant disease-free survival (DDFS) was 87.2% and the overall survival (OS) was 91%. Only T stage and nodal status at baseline were found to be significantly associated with survival estimates. CONCLUSION: The anthracycline-free regimen TCH is effective and safe in the neoadjuvant therapy of HER2-positive breast cancer, yielding DFS, DDFS and OS probabilities comparable to the results of adjuvant trials. Our data support the use of TCH as a neoadjuvant therapy regimen for patients with HER2-positive breast cancer. They also strongly encourage the use of taxanes and platinum salts as the chemotherapy backbone in studies investigating dual blockade with trastuzumab and pertuzumab in the neoadjuvant setting.

Sequential chemotherapies for advanced gastric cancer: a retrospective analysis of 111 patients.

BACKGROUND: The role of second-line chemotherapy in advanced gastric cancer is not yet fully established. PATIENTS AND METHODS: We analysed 111 patients with advanced gastric cancer treated at the University Hospital Heidelberg (51) and the private oncology practice Bottrop/Dorsten (60) between 2001 and 2011, comparing the outcome of patients with first-line chemotherapy and those who received second-line chemotherapy. RESULTS: Thirty-six patients were treated with one chemotherapy regimen, 75 patients received at least two different chemotherapies. Patients who received one chemotherapy regimen were older (median age 69 years) and had a shorter overall survival (6 months) than patients receiving sequential chemotherapies [median age 61 years, p = 0.009, overall survival 14 months (2-42), p = 0.001]. Under second-line chemotherapy, partial response was observed in 25 patients (33%) and stable disease for ≥3 months in 26 patients (35%). Patients treated before 2005 had a slightly better overall survival than patients treated in or after 2005. Survival was not influenced by the treatment centre (primary or tertiary), but was influenced by former surgery. CONCLUSION: The prognosis of advanced gastric cancer is still poor. Selected patients may benefit from individualized salvage chemotherapy after failure of first-line chemotherapy.