Real-World Clinical Outcomes of Ribociclib in Combination with a Non-Steroidal Aromatase Inhibitor and a Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal HR+/HER2- Advanced Breast Cancer Patients: An Italian Managed Access Program.

Ribociclib plus an aromatase inhibitor and ovarian function suppression is the preferred first-line option for pre-/perimenopausal women with hormone receptor-positive/human epidermal growth factor receptor-2-negative advanced or metastatic breast cancer. We opened an italian managed access program (MAP) that permitted access to ribociclib to selected patients and allowed to collect informative results on the clinical impact of the therapy. The MAP (April 2018-May 2020) included 64 premenopausal patients, with characteristics similar to those of the MONALEESA-7 trial. Of 57 patients with a known response, 48 (84.2%) achieved a clinical benefit (i.e., complete response, N = 7 (12.3%); partial response, N = 17 (29.8%); stable disease, N = 24 (42.1%)), while 9 (15.8%) experienced tumor progression. Some patients (N = 15-23.4%) needed ribociclib dose reduction because of adverse events. Thereafter, the treatment was well tolerated, and no new safety signals emerged. Our study is the first reported Italian real-world evidence of ribociclib effectiveness in premenopausal HR+/HER2- advanced breast cancer patients. Response and clinical benefit rates were particularly encouraging compared with those of the ribociclib group of MONALEESA-7. Our work confirms that ribociclib in combination with endocrine therapy is highly effective in the treatment of premenopausal HR+/HER2- advanced breast cancer patients with an expected safety profile.

Confirmed Activity and Tolerability of Weekly Paclitaxel in the Treatment of Advanced Angiosarcoma.

Background. In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with angiosarcoma. Patients and Methods. Our study was originally designed as a prospective, phase II multicenter trial for patients younger than 75, with ECOG performance status 0-2, affected by locally advanced or metastatic angiosarcoma. Patients received paclitaxel 80 mg/m(2) intravenously, at days 1, 8, and 15 every 4 weeks, until disease progression or unacceptable toxicity. Primary endpoint was objective response. Results. Eight patients were enrolled but, due to very slow accrual, the trial was prematurely stopped and further 10 patients were retrospectively included in the analysis. Out of 17 evaluable patients, 6 patients obtained an objective response (5 partial, 1 complete), with an objective response rate of 35% (95% confidence interval 17%-59%). Of note, five responses were obtained in pretreated patients. In the paper, details of overall survival, progression-free survival, and tolerability are reported. Conclusions. In this small series of patients with locally advanced or metastatic angiosarcoma, weekly paclitaxel was confirmed to be well tolerated and active even in pretreated patients.

Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study.

OBJECTIVE: According to experimental findings, oxycodone (OX) could have some advantages over morphine (MO) in clinical models of visceral pain. It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain. METHODS: Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study. Patients were randomized to receive 30 mg/d of sustained release oral MO or sustained release oral OX (20 mg/d). Opioid doses were increased according to the clinical needs. Daily doses of opioids, pain and symptom intensity were recorded at admission (T0) and at weekly intervals for the subsequent 4 weeks (T1, T2, T3, and T4), with an extension at 8 weeks (T8). Opioid escalation index (OEI) as percentage (OEI %) and in mg (OEI mg) was calculated. RESULTS: Nineteen and 20 patients in groups OX and MO, respectively, were followed for the entire period of study (T4). No differences between groups were found in age (P=0.400), Karnofsky (P=0.667), or escalation indexes at T4 and T8 (OEImg, P=0.945 and OEI %, P=0.295). No statistical differences in pain and symptoms intensity between the groups were observed. CONCLUSION: OX and MO provided similar analgesia and adverse effects with similar escalating doses in patients with pancreatic cancer pain, resembling observations reported in the general cancer pain population. The experimental hypothesis that OX would be superior to MO in the clinical model of pancreatic cancer pain was not confirmed.

Breakthrough pain in oncology: a longitudinal study.

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.

Irinotecan plus bolus/infusional 5-Fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale.

BACKGROUND: Patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy are still in relatively good clinical conditions and may still require second-line chemotherapy, which is frequently administered in daily clinical practice given to without solid scientific support. PATIENTS AND METHODS: A retrospective survey was carried out including 40 patients with stage III or IV gemcitabine-refractory pancreatic carcinoma. Patients received standard FOLFIRI regimen biweekly until progression or unacceptable toxicity. Response evaluation criteria in solid tumors and National Cancer Institute common toxicity criteria were employed respectively for response and toxicity assessment. RESULTS: Six partial responses (15%) and 14 stabilizations of disease (35%) were recorded for a tumor growth control rate of 50%. The median time to progression was 3.7 (range, 1-6.5 months), and median overall survival was 6 months (range, 2-8.2 months). A stabilization of performance status and a subjective improvement of cancer-related symptoms were recorded in 21 patients (52.5%). No correlation has been found between length of time to progression during first-line chemotherapy and length of that reported in the second-line setting or objective response. Grade 3-4 diarrhea and mucositis was observed in 15% and 10% of cases, respectively. CONCLUSIONS: Data presented in this article demonstrate that the second-line FOLFIRI regimen are able to induce an objective response in a relatively small fraction of patients with gemcitabine-refractory adenocarcinoma of the pancreas. The use of second-line chemotherapy should be carefully proposed to patients with good performance status or those who had a good response to first-line therapy.

MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.

BACKGROUND: The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. PATIENTS AND METHODS: MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). RESULTS: Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy. CONCLUSION: Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better defined.

A case of squamocellular uterine cervix carcinoma metastatic to the skin with enterocutaneous fistula.

Metastases to the skin complicated by enterocutaneous fistula are a rare event in gynecological malignancies. We present the case of a 70-year-old woman with uterine cervix carcinoma metastatic to the skin and treated with surgery and radiotherapy. The last relapse to the skin was complicated by the formation of an enterocutaneous fistula. This low-output fistula was treated with surgery and adequate supportive care. The treatment of enterocutaneous fistulas may be either invasive (surgical resection, surgical repair with corrective procedures or with myocutaneous flaps, colonic and/or urinary diversion, endoscopic treatments with metallic stents) or conservative (skin care and local disinfection, pouching of secretions, control of nutrition and electrolytes, TPN, antisecretory treatment with scopolamine or octreotide, and control of psychological conditions). Enterocutaneous fistulas associated with skin metastases are not commonly reported in the literature and may be successfully treated with surgery and supportive care in patients with good performance status and no evidence of further metastatic disease.

Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases.

BACKGROUND: The effects of the bisphosphonate derivative zoledronic acid (ZA) on the circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in patients with bone metastasis (BMTS) and the possible correlation with the symptomatic response induced by this drug in these patients were evaluated. PATIENTS AND METHODS: Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the plasma of 30 patients with painful bone metastases from breast or prostate cancer undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects (HS) of both genders (12 female and 30 male) served as the control group. The symptomatic response to ZA was assessed by the visual analog scale score (VAS). RESULTS: The median MMP-2 and MMP-9 pretreatment levels were more elevated in BMTS as compared to HS (p < or = 0.0001). Conversely, uPA levels were lower in BMTS p = 0.0033; no significant difference was observed for Cath B. ZA administration was associated with a symptomatic response (VAS score < or =4) in 25/30patients (83.3%) (p < 0.0001). This phenomenon paralleled a decrease of Cath B and MMP-2 plasma concentrations from baseline values on week 12 (p = 0.05). A similar trend, although not statistically significant, was also noted for MMP-9 and uPA. However, no direct relationship was observed between the analgesic effect induced by ZA and changes in the circulating levels of these enzymes. CONCLUSION: These data show that ZA administration may provide relief from bone pain in patients with diffuse skeletal metastases and confirm a possible implication of cysteine proteinases and matrix metalloproteinases in bone metastasis formation, but not in the pathogenesis of metastatic bone pain.

Managing cancer patients with acute venous thromboembolism: exploring safe alternatives to hospitalisation.

Acute venous thromboembolism (VTE) is a common and potentially fatal complication that frequently occurs in cancer patients. Few data are currently available about the optimal management of this category of high-risk patients. In clinical practice, physicians have to deal with many problems related to cancer patients with acute VTE. For instance, cancer patients with deep vein thrombosis (DVT) are frequently admitted to the hospital since their high rate of recurrent thrombotic events and/or bleeding-related therapy; however, most of them would prefer alternatives to prolonged hospitalisation. Then, it is not clearly whether data coming from a non-cancer population (such as that regarding the use of D-dimer test and/or pre-test clinical probability [PCP]), can be reliable applied in cancer patients. Finally, scanty information is present on the feasibility of the "home-treatment program" for DVT in this category of high-risk patients. In our review we present data on a population of cancer patients evaluated at the Emergency Care in whom we have evaluated: 1) the diagnostic accuracy of PCP and D-dimer test; 2) the safety and efficacy of low molecular weight heparins (LMWH) as "protective anticoagulation" in case of deferred imaging for VTE and 3) the safety and efficacy of home treatment.