Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer.

Background: Osimertinib is an irreversible tyrosine kinase inhibitor approved for the treatment of metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). In clinical trials, osimertinib has exhibited excellent activity and less toxicity compared to gefitinib, erlotinib and standard chemotherapy. Case Presentation: Herein, we describe the case of a 69-year-old man who received first-line osimertinib for metastatic EGFR-mutated NSCLC. Suspected osimertinib-induced pancytopenia together with a partial treatment response was assessed after 10 days of therapy. Osimertinib was resumed at 40 mg daily a month later while the patient exhibited durable stable disease. No other adverse events occurred. Conclusion: In the current case, first-line treatment with osimertinib at 80 mg daily in a patient with EGFR-mutated NSCLC resulted in severe pancytopenia and a rapid treatment response. Dose reduction to 40 mg daily resulted in excellent activity without any further adverse events. Osimertinib could be safely resumed at a reduced dose even after pancytopenia.

Alectinib Induced Regression of Renal and Hepatic Cysts Caused by Crizotinib.

BACKGROUND: Crizotinib is the first tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC). An increased incidence of renal cysts has been described during the crizotinib treatment. CASE PRESENTATION: We herein report the case of a 74-year-old woman who received crizotinib for metastatic ALK-positive NSCLC. During the crizotinib treatment, complex renal cystic lesions with invasion of perirenal spaces and iliopsoas muscle appeared; two complex hepatic cysts were also observed. Almost all lesions disappeared after switching to alectinib, a second-generation ALK inhibitor. CONCLUSION: It would seem that alectinib is able to reduce in size and number hepatic and renal cysts caused by the crizotinib treatment. Nevertheless, further studies are needed to clarify the role of both crizotinib in the onset of renal and hepatic cysts and alectinib in their disappearance.

Relationship and Predictive Role of the Dual Expression of FGFR and IL-8 in Metastatic Renal Cell Carcinoma Treated with Targeted Agents.

BACKGROUND/AIM: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry. RESULTS: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047). CONCLUSION: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents.

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.

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.

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.

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.

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.

Epirubicin plus low-dose trastuzumab in HER2 positive metastatic breast cancer.

PURPOSE: This phase II study, evaluated the activity and cardiotoxicity of first-line epirubicin plus low-dose trastuzumab (LD-T) in patients with HER2 positive MBC. METHODS: Patients received epirubicin 90 mg/sqm every 3 weeks plus weekly LD-T (2 mg/kg loading dose, then 1 mg/kg). After 6/8 cycles of epirubicin, single agent trastuzumab was continued. Cardiotoxicity was defined as signs or symptoms of congestive heart failure (CHF), or >or=15% decline in LVEF without symptoms, or <15% LVEF decline to less than 50%, without symptoms. RESULTS: Forty-five patients were enrolled. Twenty-three received prior adjuvant anthracyclines. Overall response rate was 61.4%. The median time to progression was 7.4 months and the median survival was 32.8 months. Two (4.5%) patients developed CHF. CONCLUSIONS: Epirubicin plus LD-T is an active regimen, however, the relatively high rate of cardiotoxicity together with the availability of less cardiotoxic and active trastuzumab-containing combinations precludes further evaluation of this regimen.