Baseline 18F-Fluorocholine PET/CT and bone scan in the outcome prediction of patients treated with radium 223 dichloride.

AIM: To establish the utility of baseline 18F-Fluorocholine (FCH) PET/CT and bone scintigraphy (BS) in the outcome prediction of patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with 223Ra. METHODS: Prospective, multicenter and non-randomized study (ChoPET-Rad study). FCH PET/CT and BS were performed before the initiation of 223Ra (basal FCH PET/CT and BS). Bone disease was classified attending the number of lesions in baseline BS and PET/CT. FCH PET/CT was semiquantitatively evaluated. Gleason score, baseline levels of prostate-specific antigen (PSA), alkaline phosphatase and lactate dehydrogenase were determined. Progression-free survival (PFS) and overall survival (OS) since the onset of 223Ra treatment was calculated. PFS was defined by PSA rising. Relations between clinical and imaging variables with PFS and OS were evaluated by Pearson, Mann-Whitney tests and Kapplan-Meier analysis. Univariate and multivariate Cox regression analysis was performed. RESULTS: Forty patients were evaluated. The median PFS and OS were of 3.0 ± 2.3 and 23.0 ± 4.2 months, respectively. 33 patients progressed and 13 died during the follow-up. The extension of the bone disease by FCH PET/CT (p = 0.011, χ2 = 10.63), BS (p = 0.044, χ2 = 8.04), SUVmax (p = 0.012) and average SUVmax (p = 0.014) were related to OS. No significant association was found for the PFS. ROC analysis revealed significant association of SUVmax, average SUVmax and basal PSA with OS. Only therapeutic failure was associated with OS in the multivariate analysis (HR = 3.6, p = 0.04). CONCLUSION: FCH PET/CT and BS had prognostic aim in the prediction of OS. None clinical or imaging variable was able to predict the PFS, probably due to the high rate of progressive disease.

Real-world data on the efficacy and safety of weekly oral vinorelbine in breast cancer patients previously treated with anthracycline or taxane-based regimens.

PURPOSE: To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2 for metastatic breast cancer (MBC) in patients previously treated with anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS: Fifty-five patients were enrolled in a prospective multicentre study conducted in Spain. Women ≥ 18 years of age with locally advanced breast cancer who were not candidates for surgical treatment with a radical intention or patients with stage IV disease, and who had received a prior taxane or anthracycline regimen were eligible for participation. RESULTS: Median age was 67 years. Median progression-free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1% and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%, febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients received complete treatment without delays or dose reduction. Moreover, HER2-positive patients who received oral vinorelbine concomitantly with trastuzumab showed better response (complete response: HER2-positive 14.3% vs. HER2-negative 0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008), better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p = 0.011), and better values for the remaining analysed variables than HER2-negative patients. CONCLUSION: Our study provides real-world data on the use of oral weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC patients previously treated with taxanes or anthracyclines. Patients with HER2-positive disease could also benefit from this treatment in combination with trastuzumab.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.

Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours

PURPOSE: To estimate the cost per skeletal-related event (SRE) in patients with bone metastases secondary to solid tumours in the Spanish healthcare setting. METHODS: Patients diagnosed with bone metastases secondary to breast, prostate or lung cancer were included in this multicentre, observational study. SREs are defined as pathologic fracture (vertebral and non-vertebral fracture), radiation to bone, spinal cord compression or surgery to bone. Health resource utilisation associated with these events (inpatient stays, outpatient, emergency room and home health visits, nursing home stays and procedures) were collected retrospectively for all SREs that occurred in the 97 days prior to enrolment and prospectively during follow-up. Unit costs were obtained from the 2010 eSalud healthcare costs database. RESULTS: A total of 93 Spanish patients with solid tumours were included (31 had breast cancer, 21 prostate cancer and 41 lung cancer), contributing a total of 143 SREs to this cost analysis. Inpatient stays (between 9.0 and 29.9 days of mean length of stay per inpatient stay by SRE type) and outpatient visits (between 1.7 and 6.4 mean visits per SRE type) were the most frequently reported types of health resources utilised. The mean cost per SRE was between 2,377.79 (radiation to bone) and 7,902.62 (spinal cord compression). CONCLUSION: SREs are associated with a significant consumption of healthcare resources that generate a substantial economic burden for the Spanish healthcare system (AU)

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Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours.

PURPOSE: To estimate the cost per skeletal-related event (SRE) in patients with bone metastases secondary to solid tumours in the Spanish healthcare setting. METHODS: Patients diagnosed with bone metastases secondary to breast, prostate or lung cancer were included in this multicentre, observational study. SREs are defined as pathologic fracture (vertebral and non-vertebral fracture), radiation to bone, spinal cord compression or surgery to bone. Health resource utilisation associated with these events (inpatient stays, outpatient, emergency room and home health visits, nursing home stays and procedures) were collected retrospectively for all SREs that occurred in the 97 days prior to enrolment and prospectively during follow-up. Unit costs were obtained from the 2010 eSalud healthcare costs database. RESULTS: A total of 93 Spanish patients with solid tumours were included (31 had breast cancer, 21 prostate cancer and 41 lung cancer), contributing a total of 143 SREs to this cost analysis. Inpatient stays (between 9.0 and 29.9 days of mean length of stay per inpatient stay by SRE type) and outpatient visits (between 1.7 and 6.4 mean visits per SRE type) were the most frequently reported types of health resources utilised. The mean cost per SRE was between 2,377.79 (radiation to bone) and 7,902.62 (spinal cord compression). CONCLUSION: SREs are associated with a significant consumption of healthcare resources that generate a substantial economic burden for the Spanish healthcare system.

Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study.

Thirty-four patients with metastatic breast cancer (MBC) who had progression of disease after high-dose chemotherapy (HDCT) with peripheral blood progenitor cell support (PBPC) had methotrexate, uracil and tegafur (UFT), and leucovorin (MUL) therapy administered: methotrexate administered intramuscularly in combination with UFT given orally and leucovorin given orally. All patients had received extensive prior chemotherapy including a high-dose regimen with PBPC support. Two complete responses (CR) and 11 partial responses (PR) were observed (objective response rate: 13/34 or 38%, 95% confidence interval 22-56%). Seven additional patients had stable disease (SD), 4 of whom (12% of the total population) of 6 months or longer duration, with the clinical benefit rate (CR + PR + SD of at least 6-month duration) reaching 50%. Median follow-up was 38 months, and the median time to progression and the median overall survival time from the start of MUL were 5.5 and 11 months, respectively. Toxicity was mainly gastrointestinal. Eight patients (24%) had World Health Organization grade II or greater diarrhea and/or enteritis and, consequently, the UFT dose was reduced. Emesis was mild and easily manageable with thiethylperazine given orally. The regimen did not produce significant myelosuppression or alopecia. In conclusion, patients with MBC retain chemosensitivity even when they progress after HDCT/PBPC and can be treated again with chemotherapy. MUL is active and well tolerated in patients with MBC progressing after HDCT. Further studies with this regimen, as salvage chemotherapy or as maintenance chemotherapy after HDCT/PBPC, would appear to be warranted.

Paclitaxel plus vinorelbine in metastatic breast Ca patients with contraindications to receive anthracyclines.

Thirty-three metastatic breast cancer patients with prior chemotherapy (adjuvant alone, 9 patients; chemotherapy for metastatic disease alone, 13 patients; chemotherapy for both, 11 patients) received paclitaxel (Taxol) 135 mg/m2 over 1 h followed by vinorelbine (Navelbine) 30 mg/m2 over 10 minutes on day 1 every 3 weeks. All patients had contraindications to receive anthracycline therapy (primary resistance, 10 patients; dose reaching the maximum recommended dose and/or myocardiopathy, 23 patients). Twenty-eight patients had previously received anthracyclines, and the remaining 5 had received prior CMF (cyclophosphamide, methotrexate, fluorouracil). The combination of paclitaxel plus vinorelbine was given as first-line chemotherapy for metastatic disease to 9 patients and as second- or third-line to the remaining 24 patients. The mean number of metastatic sites was 2 (range 1-5). Twenty-two patients had visceral involvement. Overall, 3 complete and 13 partial responses were observed among the 33 patients (objective response rate 48.5%, 95% confidence interval 31% to 66.5%). The response rate in patients receiving the regimen as first-line chemotherapy was 67% (6/9 patients), compared to 42% (10/24) in those receiving the regimen as second- or third-line chemotherapy. Primary anthracycline-resistant patients showed a response rate of 60% (6/10), whereas the remaining patients had a response rate of 43.5% (10/23). The main toxicities were grade 3 alopecia (92%), grade 3-4 neutropenia (28%), neutropenic fever (16%), grade 1-2 peripheral neuropathy (44%), arthralgias-myalgias (32%), and hypersensitivity reactions (8%). Phlebitis was a significant clinical problem in patients receiving the drugs through a peripheral vein.

Neoadjuvant therapy with cisplatin/fluorouracil vs cisplatin/UFT in locally advanced squamous cell head and neck cancer.

This study compared the activity and toxicity of fluorouracil (5-FU)/ cisplatin with the combination tegafur and uracil (UFT)/cisplatin in the neoadjuvant treatment of locally advanced-stage III or IV (MO)-head and neck cancer. A total of 67 patients were randomly assigned to treatment with cisplatin 100 mg/m2 on day 1 followed by either a continuous infusion of 5-FU 1,000 mg/m2/day on days 2 through 6 (group 1) or oral administration of UFT 300 mg/m2/day on days 2 through 20 (group 2). Both treatments were repeated every 21 days for four cycles. Responding patients received locoregional standard radiotherapy (50 to 70 Gy) after chemotherapy. Group 1 was comprised of 34 patients, 30 of whom were men, with a median age of 57.5 years; 79% of this group had a Karnofsky performance status of 90% to 100%; 70% had a squamous and 29% an undifferentiated histology. The majority (85%) had stage IV disease. Of the 33 patients in group 2, 29 were men. The median age was 56 years. Most (88%) had a performance status of 90% to 100%. More patients had a squamous than an undifferentiated histology (82% vs 18%) and most (88%) had stage IV disease. Overall response in group 1 was 73% (21% complete) compared with 79% (18% complete) in group 2. At a median follow-up of 84 months, no significant differences have emerged in overall survival, 15 vs 37 months, or time to progression, 8.5 vs 14.5 months, for groups 1 and 2, respectively. Toxicity was also similar, except for phlebitis, which occurred significantly more often in group 1 (71% vs 9%). Cisplatin/UFT was as effective as the classic cisplatin/5-FU regimen and has the advantages of outpatient oral administration and a lower incidence of phlebitis.