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BackgroundBone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC.Patients and methodsData on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed.ResultsMedian time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; PConclusionsRCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

PurposeTo evaluate bone density changes at the level of normal bone and bone metastases after zoledronic acid (ZA) treatment in oncologic patients.Materials and methodsWe retrospectively evaluated 72 consecutive adult patients with histologically confirmed solid tumors with at least 1 newly diagnosed bone metastatic lesion. Bone metastases were diagnosed by bone scans and confirmed with computed tomography (CT). Patients received intravenous ZA, 4mg, by 15-min infusion every 28 day through a peripheral or a central venous access and were monitored for at least 3 months and a maximum of 24 months. Bone density was determined at the level of bone metastases and at the level of normal trabecular and cortical bone using a ROI-based approach.ResultsA significant increase was demonstrated at the level of normal trabecular bone of the calvarium and the femoral neck. No significant increase of density was observed at the level of the normal cortical bone. Bone metastases showed a significant increase in CT density as compared to baseline up to 24 months after zoledronic acid.ConclusionWe have found that long term treatment with ZA increases trabecular bone density in oncologic patients whereas normal cortical bone changes are not detectable.

Background Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. Patients and methods This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. Results Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P = 0.009) and produced a trend toward improved overall survival versus no zoledronic acid. Conclusion This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.

Context Existing studies on breakthrough pain (BP) have reported different prevalence rates because of different settings, populations, and assessment methods. These studies have used cross-sectional designs, and the relationship of BP with analgesic treatment has not been evaluated. Objectives The aim of this study was to longitudinally assess BP in cancer patients admitted to oncology units. Methods A consecutive sample of patients admitted to oncology centers was selected. At admission (T0), three months after admission (T3), and six months after admission (T6), data on background pain and BP were recorded. BP was assessed in terms of its intensity, duration, number of episodes, onset with movement, spontaneous relief after stopping activity, limitation of physical activity, and effectiveness of analgesics. Results Three hundred two patients completed the study. At T0, T3, and T6, 39%, 38%, and 33% patients, respectively, had continuous pain (P=0.294). Pain intensity significantly decreased (P=0.004 and 0.027 at T3 and T6, respectively). Most patients had BP at T0 (87.1%), T3 (80.9%), and T6 (73.2%), and there was a significant decrease in the prevalence of BP over time (P=0.016). Of 149 patients with BP, pain on movement was recorded in 43.6%, 43.4%, and 32.4% at T0, T3, and T6, respectively (P=0.228). Pain spontaneously decreased or ceased when stopping physical activity in 66%, 56%, and 62% at T0, T3, and T6, respectively (P=0.537). Pain on movement strongly limited physical activity in most patients. Conclusion These data expand current information about BP and underline the need for a longitudinal assessment of a phenomenon that is invariably dependent on stage of disease, patient, and therapeutic factors.

New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

e15530 Background: The aims of this phase II trial are to determine the activity and the safety of the new combination modality with Gemcitabine fixed dose rate (FDR) infusion and Capecitabine in patients with advanced pancreatic cancer. Methods: Patients with unresectable pancreatic cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Gemcitabine (800 mg/mq IV infused in 80 minutes on days 1 and 8) and Capecitabine (650 mg/mq orally twice daily for 14 days) were administered and repeated every 21 days. Results: 47 patients were enrolled between January 2004 and October 2008. Median age was 66 (range: 37–79), 18 female and 29 male. A total of 299 cycles were administered, median cycles for patient were 6 (range: 1–17). CR was observed in one patient (2.1 %) and 10 patients achieved PR (21.3 %) giving an overall response rate of 23.4 % in intention-to-treat population. 22 pts (46.8 %) had stable disease obtaining an overall tumour control of 70.2 %. The median time to progression was 5.2 months (95 % CI, 2.4–7.6); the median overall survival was 8.4 months (95 % CI, 5.5–20). Grade 3–4 neutropenia was observed in 29.8 % of subjects, thrombocytopenia in 6.4 %. Grade 1–2 non-hematological toxicities were asthenia (61.7 %), diarrhea (29.8%), stomatitis (29.8 %) and hand foot syndrome (2.1 %). There were no treatment-related deaths. Gemcitabine was skipped at least once/reduced in 51/10.6 % of the patients, respectively. Capecitabine was skipped at least once/reduced in 16/8 % of the patients, respectively. Conclusions: The combination of FDR Gemcitabine and Capecitabine with this modality of infusion is feaseble, safe and seems to be active. No significant financial relationships to disclose.

Background Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. Methods Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. Results A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%–56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 – 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 – 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 – 11.82). Conclusion OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.