Predictive Value of Early Skin Rash in Cetuximab-Based Therapy of Advanced Biliary Tract Cancer.

Randomized trials in advanced biliary tract cancer (BTC) did not show benefit of cetuximab addition over chemotherapy. This is probably due to the lack of predictive biomarkers. The aim of this study was to explore possible predictive factors. Between 2009 and 2014, 57 patients were treated in 3-week cycles with cetuximab (250 mg/m2/week, loading dose: 400 mg/m2), gemcitabine (1000 mg/m2 on day 1 and 8), and capecitabine (1300 mg/m2/day on days 1-14). The objective response rate (ORR), progression-free (PFS) and overall survival (OS) and the adverse events (AEs) were evaluated. An exploratory analysis was performed to find possible predictive factors on clinicopathological characteristics, routine laboratory parameters and early AEs, which occurred within 2 months from the beginning of treatment. The ORR was 21%. The median PFS and OS were 34 (95% CI: 24-40) and 54 (43-67) weeks, respectively. The most frequent AEs were skin toxicities. In univariate analysis performance status, previous stent implantation, thrombocyte count at the start of therapy, early neutropenia and skin rash statistically significantly influenced the ORR, PFS and/or OS. In multivariate Cox regression analysis only normal thrombocyte count at treatment start and early acneiform rash were independent markers of longer survival. In patients showing early skin rash compared to the others the median PFS was 39 vs. 13 weeks and the median OS was 67 vs. 26 weeks, respectively. It is suggested that early skin rash can be used as a biomarker to select patients who would benefit from the treatment with cetuximab plus chemotherapy.

A comparative analysis on the efficacy and safety of intaxel® and taxol® in advanced metastatic breast cancer.

BACKGROUND: Among the presently available cytotoxic drugs, paclitaxel, in combination with doxorubicin and carboplatin, come under the highly active therapy for metastatic breast cancer. Between the two brands of paclitaxel (Intaxel, which is marketed by Fresenius Kabi and Taxol, the original paclitaxel which is manufactured by BMS) the similarity has not been evaluated in clinical trial settings till date. This prospective, controlled, randomized, multicentre, open-label phase IV study was planned to compare the safety and efficacy of Intaxel with Taxol, when they were used in combination with carboplatin or doxorubicin, as a second line treatment for metastatic breast cancer. METHODS: Fourty nine eligible patients were randomized to receive Intaxel or Taxol with either doxorubicin or carboplatin. The patients who had received a prior anthracycline based chemotherapy were randomized to the paclitaxel/carboplatin arm. The patients were evaluated in three phases i.e. at baseline, during the treatment and at follow up for the tumour response, the time period till the disease progression and the toxicity. The time till the disease progression was assessed by the Kaplan-Meier method. The continuous and categorical variables were assessed by using the ANOVA test and Fisher's exact test, respectively. RESULTS: After 3 cycles, an objective response rate of 55.56% (CR = 3, PR = 7) was noted in the Intaxel group and that of 59.09% (CR = 1, PR = 12) was noted in the Taxol group. After 6 cycles, an objective response rate of 50% was noted in both the groups. No significant difference was observed in the response rate of the two groups after 3 cycles (p > 0.05) and at the end of the treatment (p > 0.05). The patients who received Intaxel had a lower incidence of thrombocytopaenia (p = 0.0146) and neurosensory loss (p = 0.008) as compared to those who received Taxol. CONCLUSION: The results of this study demonstrated that the safety and efficacy of Intaxel and Taxol are equivalent when they are used in combination with other cytotoxic agents as the second line of treatment for metastatic stage IV breast cancer.

Inflammatory breast cancer-comparing the effectivity of preoperative docetaxel-epirubicine protocol to conventional antracycline-containing chemotherapy to achieve clinical benefit and complete pathological response.

Our retrospective analysis compared the effectiveness of conventional antracycline-containing protocols (A+) and docetaxel/epirubicine (TE) as primary systemic chemotherapies (PSCT) for inflammatory breast cancer (IBC). Seventy IBC patients received either A + (n = 48) or TE (n = 22) as PSCT. The objective clinical response and clinical benefit rate of treated patients were 54.3% (A+: 54,2% vs. TE: 54,5%; p = 0,28) and 92.8% (A+: 91,7% vs. TE: 95,5%; p = 0,57), respectively. The clinical complete response rate (cCR) was 23.2% (A+: 27,1% vs. TE:4,5%; χ (2) = 4,79; p = 0,03) with 7.14% (A+: 10,4% vs. TE:0%; χ (2) = 2,47; p = 0,12) of pathological complete responses (pCR). The median progression free (PFS)/local progression free (LPFS)/overall survival (OS) was 2.0/5.4/4.0 years, respectively. Patients achieving cCR had a tendency for better survival parameters than patients with less than cCR. Response rates or survival data were not statistically different in the two chemotherapy (CT) treatment groups. The survival was not influenced by the number of CT cycles in either protocols. In this set of patients, the clinical efficacy of the two alternative primary systemic chemotherapies (A + and TE) is equivalent in the treatment of inflammatory breast cancer (IBC), despite of the significant difference in favour of A + noticed in CRs. Six cycles of CT could be enough for patients achieving CR, however sequential pre- and/or postoperative CT with non cross-resistant drugs should be considered for non-responders.

[Changes in renal function during bisphosphonate treatment of breast cancer patients]. / A biszfoszfonát-kezelés során észlelheto vesefunkció-változás vizsgálata emlorákos betegeinknél.

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.