Sunitinib versus pazopanib para el tratamiento del carcinoma de células renales metastásico: experiencia en 2 hospitales turcos / Sunitinib versus pazopanib for patients with metastatic renal cell carcinoma: 2 Turkish hospital experience

INTRODUCCIÓN: Sunitinib (SUN) y pazopanib (PAZ) son 2 inhibidores orales de la tirosina cinasa que actúan contra el factor de crecimiento endotelial vascular. Su eficacia y seguridad en el carcinoma de células renales metastásico se ha demostrado con estudios de fase III. Sin embargo, la evidencia real es escasa. El objetivo de este análisis es evaluar el beneficio clínico de SUN y PAZ en la práctica clínica habitual. MÉTODOS: Revisamos los registros médicos de 79 pacientes con carcinoma de células renales metastásico tratados con SUN (50 mg/día en el régimen 4/2) o PAZ (800 mg/día continuo). Los pacientes fueron evaluados retrospectivamente en 2 hospitales turcos entre 2006 y 2016. RESULTADOS: La mediana de edad de toda la cohorte fue de 60 (28-87) años y el 70% de ellos eran hombres. La tasa de respuesta objetiva y la tasa de control de la enfermedad en los grupos SUN/PAZ fueron 34/37% (p = 0,96) y 78/87% (p = 0,046), respectivamente. Con una mediana de seguimiento de 15 meses, las medianas de supervivencia libre de progresión y de supervivencia global en los grupos SUN/PAZ fueron de 8/8 meses (p = 0,83) y 22/21 meses (p = 0,53), respectivamente. La toxicidad común entre SUN vs. PAZ incluía fatiga (59 vs.74%), cambios en la piel (44 vs.44%), anemia (35 vs.42%), hipotiroidismo (37 vs.19%; p = 0,02) e hipertensión (33 vs.50%). En los pacientes tratados con SUN, la toxicidad total de grado 3-4 (número medio de eventos tóxicos por paciente) fue de 0,71, mientras que en los pacientes tratados con PAZ, la toxicidad total de grado 3-4 fue de 0,11 (p < 0,001). SUN se asoció con una mayor incidencia de fatiga de grado 3-4 (p = 0,007), anemia (p = 0,001) e hipotiroidismo, requiriendo tratamiento (p = 0,02). Fue necesario reducir la dosis en los grupos SUN y PAZ en el 49 y el 24% de los pacientes (p = 0,02), y el cese del tratamiento en el 37 y el 26% de los pacientes (p = 0,37), respectivamente. CONCLUSIONES: En nuestro estudio no hubo diferencias en términos de supervivencia entre los 2 agentes. Sin embargo, en los pacientes tratados con SUN se dieron más eventos adversos de grado 3-4, siendo necesaria la reducción de la dosis

INTRODUCTION: Sunitinib (SUN) and pazopanib (PAZ) are 2 oral tyrosine kinase inhibitors against vascular endothelial growth factor. Their efficacy and safety in metastatic renal cell carcinoma has been proven with phase III studies. However, real world data is limited. The objective of this study is to assess the clinical benefit of SUN and PAZ in routine practice. METHODS: We reviewed the medical records of 79 metastatic renal cell carcinoma patients treated with SUN (50 mg/day on 4/2-schedule) or PAZ (800 mg/day continuously). Patients were assessed retrospectively at 2 Turkish hospitals between 2006 and 2016. RESULTS: For the entire cohort median age of patients was 60 (28-87) years and 70% of them were male. The objective response rate and disease control rate in SUN/PAZ groups were 34/37% (P = .96) and 78/87% (P = .046), respectively. With a median follow up duration of 15 months, median progression-free survival and overall survival in SUN/PAZ groups were 8/8 months (P = .83) and 22/21 months (P = .53), respectively. The common all grade toxicities for SUN vs. PAZ were fatigue (59 vs.74%), skin changes (44 vs.44%), anemia (35 vs.42%), hypothyroidism (37 vs.19%; P = .02) and hypertension (33 vs.50%). In patients treated with SUN, total grade 3-4 toxicities (mean number of toxic events per patients) were 0.71, whereas in patients treated with PAZ, total grade 3-4 toxicities were 0.11 (P < .001). SUN was associated with an increased incidence of grade 3-4 fatigue (P = .007), anemia (P = .001) and hypothyroidism that needed therapy (P = .02). Dose reduction in 49 and 24% of patients (P = .02), and treatment cessation in 37 and 26% of patients (P = .37) were required in the SUN and PAZ groups, respectively. CONCLUSIONS: In our study, there was no difference in terms of survival outcomes between 2 agents. However, patients treated with SUN had more grade 3-4 adverse events which prompted dose reduction

Sunitinib versus pazopanib for patients with metastatic renal cell carcinoma: 2 Turkish hospital experience. / Sunitinib versus pazopanib para el tratamiento del carcinoma de células renales metastásico: experiencia en 2 hospitales turcos.

INTRODUCTION: Sunitinib (SUN) and pazopanib (PAZ) are 2 oral tyrosine kinase inhibitors against vascular endothelial growth factor. Their efficacy and safety in metastatic renal cell carcinoma has been proven with phase iii studies. However, real world data is limited. The objective of this study is to assess the clinical benefit of SUN and PAZ in routine practice. METHODS: We reviewed the medical records of 79 metastatic renal cell carcinoma patients treated with SUN (50mg/day on 4/2-schedule) or PAZ (800mg/day continuously). Patients were assessed retrospectively at 2 Turkish hospitals between 2006 and 2016. RESULTS: For the entire cohort median age of patients was 60 (28-87) years and 70% of them were male. The objective response rate and disease control rate in SUN/PAZ groups were 34/37% (P=.96) and 78/87% (P=.046), respectively. With a median follow up duration of 15 months, median progression-free survival and overall survival in SUN/PAZ groups were 8/8 months (P=.83) and 22/21 months (P=.53), respectively. The common all grade toxicities for SUN vs. PAZ were fatigue (59 vs. 74%), skin changes (44 vs. 44%), anemia (35 vs. 42%), hypothyroidism (37 vs. 19%; P=.02) and hypertension (33 vs. 50%). In patients treated with SUN, total grade 3-4 toxicities (mean number of toxic events per patients) were 0.71, whereas in patients treated with PAZ, total grade 3-4 toxicities were 0.11 (P<.001). SUN was associated with an increased incidence of grade 3-4 fatigue (P=.007), anemia (P=.001) and hypothyroidism that needed therapy (P=.02). Dose reduction in 49 and 24% of patients (P=.02), and treatment cessation in 37 and 26% of patients (P=.37) were required in the SUN and PAZ groups, respectively. CONCLUSIONS: In our study, there was no difference in terms of survival outcomes between 2 agents. However, patients treated with SUN had more grade 3-4 adverse events which prompted dose reduction.

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE: We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc). METHODS: The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test. RESULTS: Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non-clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001). CONCLUSIONS: Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.

Impaired coronary flow reserve in metastatic cancer patients treated with sunitinib.

PURPOSE: Hypertension is one of the major side effects of sunitinib, an angiogenesis inhibitor used in the treatment of metastatic renal cell carcinomas (mRCC) and gastrointestinal stromal tumors (GIST). Endothelial dysfunction, an early and reversible event in the pathogenesis of atherosclerosis, is suggested to be one of the possible underlying mechanisms of hypertension caused by angiogenesis inhibitors. Coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in mRCC and GIST patients under sunitinib treatment. METHODS: Eighteen metastatic cancer patients (16 mRCC and 2 GIST) on sunitinib treatment and 27 healthy subjects were enrolled in this cross-sectional study. Thyroid stimulating hormone (TSH), lipid profile, creatinine, hemoglobin, glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anthropometric and physical parameters of patients were recorded. CFR recordings were performed by the Vivid 7 echocardiography device. RESULTS: CFR was significantly lower in patients when compared with controls (1.82±0.4 vs 2.71±0.8, respectively; p < 0.001). Impaired CFR was found in 13 (72%) patients whereas all controls had normal CFR values. CFR was inversely correlated with the duration of sunitinib treatment (r=-0.36, p =0.01), high sensitivite (hs) CRP (r = -0.574, p =0.01) and ESR (r = - 0.5, p = 0.02). CONCLUSION: Our findings indicate that CFR is significantly impaired in cancer patients on sunitinib treatment. There is an inverse correlation between CFR and duration of sunitinib treatment and inflammation markers.

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC)

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects (AU)

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects.

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples.

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.

Remitting seronegative symmetrical synovitis with pitting oedema associated with chronic lymphocytic leukaemia.

We describe a case of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE syndrome) in a 67-year-old man. Immunophenotyping studies and histology of biopsy specimens revealed chronic lymphocytic leukaemia (CLL). Polyarthritis and oedema were revealed by small doses of corticosteroids. The association of RS3PE syndrome with rheumatological and malign disorders are discussed.