Consiglia Carella

Pharmacokinetics of Pegylated Liposomal Doxorubicin Administered by Intraoperative Hyperthermic Intraperitoneal Chemotherapy to Patients with Advanced Ovarian Cancer and Peritoneal Carcinomatosis

The pharmacokinetics of pegylated liposomal doxorubicin (PLD) were investigated in 17 women undergoing intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer and peritoneal carcinomatosis. HIPEC was performed immediately after completing debulking surgery, which included a number of peritonectomy procedures. PLD was injected and allowed to equilibrate in peritoneal cavity filled with 4 liters of physiological solution and stabilized at 42°C; next, the outflow line was opened and perfusion proceeded for 1 h. PLD was stable in peritoneal perfusate and plasma. During HIPEC, PLD peritoneal perfusate/plasma gradients averaged ∼600 or ≥1000 for peak concentration or area under the curve. After HIPEC, PLD plasma levels remained stable or decreased. Biopsy samples of residual normal peritoneum or ovarian carcinomatosis were collected at the end of HIPEC and were shown to contain free doxorubicin. Correlating PLD decrements in peritoneal perfusate with plasma exposure to PLD or peritoneal deposition of free doxorubicin showed that the former occurred during preperfusional equilibration of PLD in peritoneal cavity, whereas the latter occurred during 1 h of perfusion. Plasma exposure to PLD correlated negatively with the number of peritonectomy procedures performed during surgery, whereas peritoneal deposition of free doxorubicin correlated positively. Taken together, these results show that PLD administered by intraoperative HIPEC undergoes limited systemic diffusion and releases active free doxorubicin in peritoneum exposed to ovarian carcinomatosis. PLD pharmacokinetics seem to be influenced by peritonectomy procedures.

Extraordinary and prolonged Erlotinib-induced clinical response in a patient with EGFR wild-type squamous lung cancer in third-line therapy: a case report

Several small molecules, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib and afatinib, have been demonstrated to significantly improve clinical outcomes in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC), but erlotinib activity in EGFR wild-type squamous carcinoma is still highly debated. Here, we describe a prolonged and unexpected clinical response to erlotinib in a male former heavy cigarette smoker with wild-type EGFR squamous-cell cancer.

Lapatinib in second-line treatment for metastatic breast cancer: rapid clinical benefit and long-term response.

Lapatinib, an oral dual ErbB1/2 tyrosine kinase inhibitor, is effective in the treatment of metastatic breast cancer that has progressed after trastuzumab-based first-line chemotherapy. Moreover, lapatinib has been found to be effective in patients with metastatic brain involvement. Here we report the case of a 55-year-old woman with metastatic breast cancer and brain metastasis who achieved rapid symptom improvement and long-term disease control.

Skin toxicity evaluation in patients treated with cetuximab for metastatic colorectal cancer: a new tool for more accurate comprehension of quality of life impacts

Objectives The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab. Methods Cutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman’s rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring. Results A positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity. Conclusion There is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system.

Immunotherapy and Hypophysitis in the Clinical Practice: A Case Report

The reported frequency of ipilimumab-induced hypophysitis (IIH), a cytotoxic T-lymphocyte antigen 4 antibody, ranges from 0 to 17%, in contrast to the rarity of idiopathic autoimmune hypophysitis that has an estimated incidence of one in nine million people per year. Here we present the case of a patient with ipilimumab- induced hypophysitis (IIH). After his third course of ipilimumab, the patient began to present worsening asthenia and severe headache. A brain MRI scan showed the mild swelling of the anterior pituitary gland and thickening of the stalk. Haematological reports were consistent with hypophysitis diagnosis: in fact, ACTH and cortisol levels were very low. Then ipilimumab was interrupted and therapy with a large dose of glucocorticoids (dexamethasone) was promptly started. A rapid symptoms improvement was obtained by this therapeutic approach. The dose of dexamethasone was gradually decreased over 4 weeks and hydrocortisone replacement was started. Development of IIH is associated with the risk of acute adrenal insufficiency or adrenal crisis, so early recognition and therapeutic intervention are extremely relevant. Furthermore, in the absence of data demonstrating clinical benefit from high-dose glucocorticoid therapy, we wondered if, in absence of symptoms such as visual disturbances or other life-threatening simultaneous irAEs in other organs, there is the indication to start with hydrocortisone replacement therapy alone from the beginning. We also wondered if it was reasonable to administer ipilimumab during prolonged high-dose glucocorticoid therapy. Thus, guidelines for surveillance and management of IH are highly required.

Rivaroxaban for Cancer-associated Cardiac Thrombosis

A 52-year-old man who was treated with the oral multitargeted receptor tyrosine kinase inhibitor sunitinib for a Fuhrman II renal carcinoma with lung metastases underwent contrast-enhanced computed tomography of the chest and abdomen for cancer response assessment. The examination revealed progression of the tumor and, concomitantly, a posterior apical mass of about 3 cm in diameter within the left ventricle compatible with cardiac thrombosis (Figure, Panel A). Magnetic resonance imaging confirmed the presence of a large mobile thrombus with no evidence of vasculature within the mass (Figure, Panels B and C). The patient had chronic dyspnea and reported no worsening of the clinical symptoms during the days preceding the scan. He received half therapeutic dose low-molecular-weight heparin (enoxaparin 1 mg/Kg/day subcutaneous once daily) for a thrombosis of the right popliteal vein, which occurred 2 years earlier during therapy with sunitinib. After confirming the intracardiac thrombotic mass, the dose of enoxaparin was increased to therapeutic levels (enoxaparin 1 mg/Kg/day subcutaneous twice daily) and sunitinib was replaced by axitinib, a second-line selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors. Despite the continuation of heparin at full therapeutic doses, the repeat contrast-enhanced computed tomography 2 months later showed enlargement of the intraventricular thrombus. Heparin was replaced with

Chemotherapy-induced nausea and vomiting in Italian cancer centers: results of CINVDAY, a prospective, multicenter study.

Purpose Guideline consistency in the prevention of chemotherapy-induced nausea and vomiting (CINV) remains low (29% in the Pan European Emesis Registry study) and very low (11%) in regimens with a high emetogenic risk. The aim of this study was to evaluate the guideline consistency of CINV prophylaxis for acute emesis in daily clinical practice in Italy. Methods This was a prospective, observational, multicenter study. Patients scheduled to receive antitumor treatment on a single prespecified day were included. Data on patient characteristics (demographic and clinical), type of anticancer therapy, and type of antiemetic therapy prescribed for acute emesis were collected on electronic data capture forms. Chemotherapy regimens and antiemetic prophylaxis were categorized according to the MASCC 2011 guidelines. The study was approved by the local ethics committees. Results From July 2013 to February 2014, a total of 502 patients were enrolled at 26 study sites. Median age was 62 years (range 27–87 years). Colorectal cancer and breast cancer were the most common malignancies. The emetogenic potential of the chemotherapy regimens used was high (HEC) (23.7%), moderate (MEC) (40.6%), low (31.3%) or minimal (4.4%). Overall, guideline consistency was 19.3%. Consistency reached 45% when the various 5HT3 receptor antagonists were considered equivalent and interchangeable in MEC regimens. Adherence to guidelines was lowest for MEC and MINIMAL risk groups. Ten percent of patients in HEC and MEC regimens did not receive any 5HT3 receptor antagonists. NK1 receptor antagonists were used in 8% of all regimens. Conclusions Our study indicates that antiemetic guideline inconsistency remains an issue in daily clinical oncology practice in Italy.