Safety evaluation of Datopotamab deruxtecan for triple-negative breast cancer: a meta-analysis.

BACKGROUND: TROP-2 is emerging as a valid and fruitful strategy in triple-negative breast cancer (TNBC) patients, and several agents are currently under evaluation, including Datopotamab deruxtecan (Dato-DXd). RESEARCH DESIGN AND METHODS: Herein, we performed a meta-analysis aimed to evaluate any grade adverse events, grade 3-4 adverse events, dose reduction, and serious adverse events in TNBC patients treated with Dato-DXd in clinical trials. RESULTS: The pooled results suggests that Dato-DXd is associated with a favorable safety profile: while any grade treatment-related toxicities were common, grade 3-4 events were not particularly frequent and mainly represented by stomatitis (13.88%; 95% CI, 10.68 - 17.09). CONCLUSIONS: These findings may help to comprehensively define the safety profile of Dato-DXd and to assist in the design of future clinical trials in this setting.

The Mediterranean Lifestyle to Contrast Low-Grade Inflammation Behavior in Cancer.

A healthy diet and an active lifestyle are both effective ways to prevent, manage, and treat many diseases, including cancer. A healthy, well-balanced diet not only ensures that the body gets the right amount of nutrients to meet its needs, but it also lets the body get substances that protect against and/or prevent certain diseases. It is now clear that obesity is linked to long-term diseases such as heart disease, diabetes, and cancer. The main reasons for people being overweight or obese are having bad eating habits and not moving around enough. Maintaining weight in the normal range may be one of the best things to avoid cancer. It has been scientifically proven that those who perform regular physical activity are less likely to develop cancer than those who lead a sedentary lifestyle. Moving regularly not only helps to maintain a normal body weight, avoiding the effects that favor tumor growth in overweight subjects, but also makes the immune system more resistant by counteracting the growth of tumor cells. Physical activity also helps prevent cardiovascular and metabolic diseases. In this review, it is highlighted that the association between the Mediterranean diet and physical activity triggers biological mechanisms capable of counteracting the low-grade chronic inflammation found in patients with cancer. This assumes that healthy lifestyles associated with cancer therapies can improve the expectations and quality of life of cancer patients.

Pemigatinib in Intrahepatic Cholangiocarcinoma: A Work in Progress.

Cholangiocarcinoma (CCA) is the second most frequent primary liver cancer, following hepatocellular carcinoma (HCC). Progress in the molecular understanding of CCA has led to the development of several agents, including FGFR inhibitors, such as pemigatinib, whose approval has marked a new era in this hepatobiliary malignancy. However, a number of questions remain unanswered, including the development of secondary resistance and the role of combination therapies, including FGFR inhibitors. Herein, we specifically focus on the current challenges and future research directions of pemigatinib use in CCA patients.

Metaplastic breast cancer: an old histotype but a current therapeutic problem.

Metaplastic breast cancer (MPBC) is a rare and aggressive tumor type in great need of satisfactory therapies. Although most cases of MPBC are 'triple negative', they are nonetheless related to worse outcomes compared with other triple-negative invasive tumors. MPBC presents high levels of genetic and molecular heterogeneity, suggesting that novel targeted therapies can be exploited. Overexpression of PD-L1 and high levels of tumor-infiltrating lymphocytes have also been observed in these tumors, suggesting a role for immunotherapy. We present an updated literature revision on clinical, histopathological and molecular features of MPBC and their significance to prognosis and therapy options. We discuss emerging efforts to improve and personalize prognostic and therapeutic approaches, exploiting the molecular signature of MPBC with targeted therapies and immunotherapies.

Sorafenib: 10 years after the first pivotal trial.

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors.

Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55-73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2-6.2) and 10.4 (95% CI, 10-11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

Management of dermatologic toxicities associated with monoclonal antibody epidermal growth factor receptor inhibitors: A case review.

INTRODUCTION: The epidermal growth factor receptor inhibitors (EGFRIs), cetuximab and panitumumab, represent an effective treatment option for patients affected by metastatic colorectal cancer (mCRC); furthermore, they are relatively devoid of systemic toxicities, which are commonly observed with standard cytotoxic chemotherapy. However, the majority of patients treated with these monoclonal antibodies (mAbs), will experience dermatologic toxicities, most notably the papulopustular skin rash, which can impact quality-of-life and affect adherence to therapy. This paper reviews the most recent practices in the management of skin rash related to anti-epidermal growth factor receptor (EGFR) mAbs, cetuximab and panitumumab, in the treatment of mCRC. MATERIALS AND METHODS: We reviewed relevant literature regarding dermatologic toxicities associated with anti-EGFR mAbs in order to give important indications about prevention and reactive treatment of skin rash. RESULTS: Two case reports were presented to show how skin rash could hamper mAb EGFRIs use in clinical practice, underscoring the need of implementing a comprehensive management strategy of skin toxicity in order to promote patients' compliance with anti-EGFR therapy and maintain quality-of-life. Based on randomized data, recent guidelines established by the Multinational Association for Supportive Care in Cancer Skin Toxicity Study Group suggest that prophylactic use of oral doxycycline or minocycline reduces the risk and severity of skin rash, improving clinical outcomes. CONCLUSIONS: At the start of treatment with cetuximab and panitumumab, the proper patient education about the skin rash associated with these mAbs and the implementation of a pre-emptive, comprehensive skin toxicity program significantly contribute to improve adherence to therapy, optimize anti-EGFR therapy and maintain quality-of-life.

Preferences of patients with advanced colorectal cancer for treatment with oral or intravenous chemotherapy.

BACKGROUND: In recent years, patient-reported outcomes such as health-related quality of life have become important areas of clinician focus in general cancer management. Patients' preferences for, and/or satisfaction with, oral versus intravenous (IV) chemotherapy schedules may have a major impact on such outcomes. OBJECTIVE: To evaluate preferences for oral or IV chemotherapy in patients with advanced colorectal cancer. METHODS: A multicenter, randomized, crossover trial was conducted in 12 hospitals in Southern Italy, in which 22 patients with advanced colorectal cancer received one cycle of oral capecitabine ± irinotecan or oxaliplatin, followed by one cycle of an IV de Gramont or similar regimen (arm A), or the same regimens in reverse order (arm B). Patients were aged 50-70 years and 21% had a higher level of education (graduate or similar). Patients received oral capecitabine 3500 mg/m/day for 7 days (± irinotecan 180 mg/m or oxaliplatin 85 mg/m on day 1 only), followed by an IV de Gramont regimen ± irinotecan (FOLFIRI) or oxaliplatin (FOLFOX); or the two schedules administered in reverse order.The main outcome measure was patients' preferences for oral versus IV chemotherapy, as determined by a pre- and post-treatment therapy preference questionnaire (TPQ). RESULTS: Before treatment, 75% of patients preferred oral therapy. Characteristics that patients considered to be important were that treatment should not interfere with daily activities (100% of patients) and should not cause fatigue (95%), diarrhea (76%), or painful mouth ulcers (76%); other factors considered important were the risk of infection and nausea (90%), and that treatment could be administered at home (65%). After receiving both chemotherapy schedules, only 45% of patients preferred oral therapy, while 55% preferred IV therapy. Among the latter, the most important characteristics influencing treatment choice were less nausea (66%), fewer mood effects (65%), the safety of hospital IV treatment (62%), less interference with family relationships (55%), less vomiting (55%), less interference with daily activities (50%), and less diarrhea (50%). Although the order in which patients received therapy did not influence treatment preference, significantly fewer patients with a lower rather than higher educational level preferred oral therapy (47% vs 80%; chi-square test = 9.9; p = 0.002). CONCLUSION: These results suggest that there may be a correlation between educational level and the preference of patients with advanced colorectal cancer for oral or IV chemotherapy.

Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma.

BACKGROUND: To the authors' knowledge, little is known to date regarding the prognostic relevance of measuring serum levels of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, in patients with colon carcinoma who undergo surgery. METHODS: Preoperative and postoperative VEGF serum levels were determined by enzyme-linked immunoadsorbent assay in 81 patients with colon carcinoma who were undergoing surgery. Fifty healthy individuals served to define normal VEGF serum levels. RESULTS: Preoperative VEGF serum levels were significantly higher in the group of patients with colon carcinoma (mean, 504.1 pg/mL +/- 223 pg/mL; range, 285-1390 pg/mL; 95% confidence interval [95%CI], 49 pg/mL) compared with the control group (mean, 78.1 pg/mL +/- 22 pg/mL; range, 40-110 pg/mL; 95%CI, 4.3 pg/mL; P < 0.001). Multiple regression analysis demonstrated a significant correlation (r) between preoperative VEGF serum levels and age (r = - 0.275; P = 0.013), Dukes stage (r = 0.488; P < 0.001), and carcinoembryonic antigen (CEA) levels (r = 0.285; P < 0.018). No significant correlation was found between preoperative VEGF serum levels and disease site, patient gender, tumor size, tumor grade, or performance status. Moreover, preoperative VEGF serum levels were significantly lower in patients who underwent curative surgery compared with patients who underwent noncurative surgery (443 pg/mL +/- 117 pg/mL vs. 821 +/- 353 pg/mL, respectively; P < 0.0001). Logistic regression analysis selected preoperative VEGF and CEA serum levels as the only good prognostic indicators of curative and noncurative surgery (P < 0.001; relative risk, 2.98 and 2.03, respectively). Furthermore, VEGF serum levels dropped significantly after surgery, with a further downward trend until the 30th postoperative day (P < 0.001). Stepwise regression analysis selected preoperative VEGF serum level as the only variable associated significantly with the prediction of both disease-specific survival and disease-free survival (P = 0.001). CONCLUSIONS: Preoperative serum VEGF levels may be useful for predicting outcome in patients with colon carcinoma who undergo surgery.

Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome.

Elevated interleukin-10 (IL-10) and IL-6 serum levels in advanced gastrointestinal cancer patients have been shown previously. To investigate the behavior and the prognostic role of IL-10 and IL-6 serum levels in gastric and colon cancer patients undergoing surgery, we studied the relationship between these cytokine levels and surgical radicality and outcome. Seventy-eight patients with gastric or colon cancer were admitted to the study, and 50 underwent radical surgery. Cytokine serum levels were measured by ELISA the day before surgery and 16 days after surgery. Circulating levels of IL-10 and IL-6 were found to be higher in cancer patients than in controls. Both IL-10 and IL-6 serum levels were demonstrated to be able to predict likelihood to perform radical surgery. IL-10 serum levels returned to normal in all but 8 radically resected patients. These 8 patients had tumor recurrence. In contrast, IL-6 serum levels were shown to significantly decrease in all patients but not to normalize regardless of the radicality of the operation. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly affecting the disease-free survival rate. Stepwise regression selected tumor stage, number of metastatic resected nodes, and basal IL-10 serum level as the best combination of variables for prediction of likelihood of tumor recurrence. Preoperative IL-10 serum levels may be a useful marker to predict likelihood of performing radical surgery. Abnormally high postoperative IL-10 values negatively affected disease-free survival and tumor recurrence. IL-6 serum levels were found to have a more limited prognostic role.

Elevated serum levels of interleukin-8 in advanced non-small cell lung cancer patients: relationship with prognosis.

Interleukin-8 (IL-8) is a pleiotropic cytokine that has also been shown to exert effects relevant to cancer growth and progression. Cancer progression is believed to be contributed to by the ability of this cytokine to promote angiogenesis and mitogenic effects. As IL-8 production at the tumor site may determine elevated serum levels of this cytokine because of hematogenous leakage, it is conceivable that patients with high IL-8 serum levels may have tumors actively producing this cytokine. The aim of this study was, therefore, to assess IL-8 serum levels in 60 non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and to correlate them with prognosis. IL-8 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, IL-8 serum levels were shown to be significantly increased in stage IV patients compared with stage III patients. When basal IL-8 serum levels in cancer patients were analyzed according to response to chemotherapy, responders were shown to have significantly lower IL-8 serum levels than nonresponders. On univariate analysis, the IL-8 serum level was included among the variables capable of affecting both overall survival (OS) and time to treatment failure (TTF). However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-8 serum levels. In conclusion, this study showed that IL-8 serum levels were elevated in advanced NSCLC patients and correlated with both OS and TTF, but they were shown not to be an independent prognostic factor.