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Lung cancer is the malignancy with the highest morbidity and mortality worldwide. Approximately 60% of non-small cell lung cancer (NSCLC) presents driver alterations most of which are targetable. Nowadays, limited clinical data are available regarding the efficacy of epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with NSCLC harboring uncommon EGFR mutations, considering their heterogeneity. Herein, we report a rare case of EGFR-mutated lung adenocarcinoma which has developed into squamous cell carcinoma with uncommon EGFR (Ex18) compound mutations and phosphatidylinositol 3-kinase mutation receiving afatinib at the forefront., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction. We conducted a multicenter retrospective observational data collection of patients with mRCC treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Univariate and multivariate analyses were performed. The aim was to describe the impact of baseline concomitant PPIs on the outcome of patients to pazopanib and cabozantinib in terms of response, progression-free survival (PFS) and overall survival (OS), toxicity, and treatment compliance. The use of PPI in our study population (301 patients) significantly influenced the effectiveness of TKIs with worse PFS (16.3 vs. 9.9 months; P < 0.001) and OS (30.6 vs. 18.4 months; P = 0.013) in patients taking PPI at TKI initiation. This detrimental effect was maintained both in the pazopanib and cabozantinib groups. The use of PPI influenced the toxicity and TKI treatment compliance with a reduction of dose or schedule modifications, and treatment interruptions in the population taking PPIs. Our study demonstrates that the use of PPIs can significantly influence the outcome and compliance of patients with mRCC to TKI treatment, suggesting the importance of a more careful selection of patients who need a gastroprotective therapy, avoiding indiscriminate use of PPIs., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: In the current study, we have investigated the effects of the different modalities of treatment (volume of radiotherapy [RT], previous surgery) as well as the Gleason score of prostate cancer (PC) on the lymphocyte composition of PC patients undergoing RT., Methods: This is a monoinstitutional study that prospectively included PC patients that underwent RT from January 2016 until December 2017. To compare the different evaluations, the Wilcoxon signed-rank test was used among 2 times (Timepoint 0 to Timepoint 1). Percentage variation was calculated for all the lymphocyte subpopulation and was correlated with clinical parameters (previous surgery, Gleason score, and pelvic irradiation) with the χ2 test. The statistical analysis was repeated also on the stratified dataset according to the above parameters (previous surgery, Gleason score, and whole pelvic radiotherapy [WPRT])., Results: One hundred and eleven patients were included in the present analysis. All the lymphocyte subpopulations resulted significantly lower after RT. The modifications of several lymphocyte subpopulations correlated with previous surgery, Gleason score, and WPRT, although stratified analysis demonstrated that WPRT showed the greatest correlation., Conclusion: Our results could be used to design a prospective trial in order to study the use of WPRT on the lymphocyte subpopulations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Lung cancer is the most common cause of cancer-related deaths worldwide. Approximately 50% of patients is metastatic at diagnosis and the most common metastatic sites are bone, lungs, brain, adrenal glands, liver, and extra thoracic lymph nodes. The occurrence of gastrointestinal metastasis from lung carcinoma is rare and seems more commonly related to small cell lung cancer compared to non-small cell lung cancer (NSCLC)., Patient Information and Diagnosis: A 78-year-old man with completely surgically resected NSCLC and no initial evidence of distant metastases developed colon and gastric metastases 7 months after diagnosis, confirmed by serial radiological examinations and endoscopic biopsies., Interventions: The patient was subjected to total gastrectomy with D2 lymph node dissection plus partial colectomy for intraoperative detection of a transverse colon neoformation. Subsequent instrumental imaging showed bilateral lung tumor recurrence, treated with gemcitabine monotherapy for 8 months as first line chemotherapy for lung adenocarcinoma., Results: The patient presented complete response to therapy and was disease-free for 4 years., Lessons: Colonic and gastric metastasis are very infrequent in NSCLC. The resection of gastrointestinal metastasis may provide benefits in terms of both symptom control and survival in patients properly selected., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer. This is a retrospective study of patients treated with ramucirumab plus paclitaxel. Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events. Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.

The aim of this report is to investigate the activity of ramucirumab in combination with paclitaxel in patients with metastatic gastric cancer (GC) and lung metastases. We retrospectively reviewed clinical data from patients with GC treated in second line with ramucirumab and paclitaxel according to the presence or not of lung metastases. Thirty-one patients were eligible. Five (16.1%) patients had lung metastases. The median progression-free survival was 156 days in patients without lung metastases compared with 54 days in patients with lung metastases. The median survival also showed a trend in favour of patients without lung metastases. Despite the small number of patients and the retrospective nature of the data, our analysis showed relatively poor efficacy of ramucirumab plus paclitaxel as a second-line treatment in patients with lung metastases from GC. Further studies are required to evaluate novel treatments in this subset of patients.

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60 mg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treated.

The aim of this study is to report first preliminary results of patients enrolled in a phase II study that will investigate the activity and safety of docetaxel, oxaliplatin, and 5-fluorouracil (DOF) in combination with trastuzumab in human epidermal receptor-2 (HER-2) positive patients with advanced gastric or gastroesophageal junction (GEJ) cancer.Treatment consisted of docetaxel 70 mg/m combined with oxaliplatin 130 mg/m on day 1, and continuous infusion 5-fluorouracil mg/m days 1-5 plus trastuzumab at the standard dose on day 1, every 3 weeks for a maximum of 8 cycles.Fifteen patients were enrolled. The overall response rate was 60%. The median progression-free survival was 9.2 months (95% confidence interval [CI], 4.4-10.1 months) and the median overall survival was 19.4 months (95% CI, 8.9-21.1 months). Grade 3 neutropenia was observed in 3 patients (20%).The DOF plus trastuzumab seems active in HER-2 positive advanced gastric or GEJ cancer, final results of the phase II study are awaited.

Background: The novel hormonal drugs have recently entered in the armamentarium of therapies for treatment of metastatic castration-resistant prostate cancer (CRPC). First reports are available for their use in elderly men with CRPC., Method: A meta-analysis of randomized controlled trials (RCTs) has been performed. PubMed, the Cochrane Library, and American Society of Clinical Oncology (ASCO) University Meeting were searched for data on the use of new hormonal treatment in elderly patients with CRPC., Results: Nine studies for a total of 3512 elderly patients were available for meta-analysis. Six studies reported outcomes of patients aged >75 years old while 2 studies reported on patients aged >70 years old. The pooled analysis of the androgen synthesis inhibitors revealed significantly increased overall survival (OS) due to antiandrogen agents compared with placebo or placebo and prednisone (hazard ratio (HR) for death: HR = 0.74, 95% CI: 0.67-0.82; P < 0.00001). Moreover, the new antiandrogenic therapy significantly improved the progression-free survival (HR = 0.45, 95% CI: 0.31-0.65; P < 0.0001). The incidence of any grade ≥3 adverse effect was only moderately higher during with the antiandrogenic therapy as compared to the control arms (response rate = 1.03, 95% CI: 0.88-1.20; P = 0.72)., Conclusion: This study confirmed that agents targeting the androgen axis (i.e., enzalutamide, abiraterone) significantly prolonged OS in elderly men with CRPC., Competing Interests: The authors have no conflicts of interest to disclose.

The oncological treatment for advanced stage head and neck cancer is based on a combination of cisplatin and cetuximab, and radiotherapy. However, very few data are available on this multimodal approach for this type of cancer in pancreas and renal recipients. We report the case of a pancreas and renal recipient being treated with combined chemoradiotherapy for a locally advanced squamous cancer of the larynx. The patient was under treatment with ciclosporin-based immunosuppressive therapy at the time of cancer diagnosis, which was then replaced by everolimus. After 4 years of follow-up, the patients is still free from disease, with a local complete response, only mild residual dysphonia, and with edema of the chin. Cetuximab plus radiation could be an adequate option for cancer treatment in solid organ transplant recipients affected by locally advanced head and neck cancer; the concomitant use of mammalian target of rapamycin pathway inhibitors may have a synergistic effect in enhancing tumor control in these patients; however, further dedicated studies are warranted.

Both abiraterone acetate (AA) and cabazitaxel (Cbz) have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel (D). Although no standard sequencing has been established as yet, Cbz has recently been proven to be active after AA. However, to date, few data are available on its safety in this setting. Therefore, the primary endpoint of this study was to investigate Cbz tolerability in mCRPC patients treated previously with D and AA. From April 2011 to the present, 43 mCRPC patients received AA after D at our institution. Of these, 22 patients were subsequently treated with Cbz and were evaluable for toxicity in the present retrospective study. Cbz was administered at a dose of 25 mg/m plus 10 mg oral prednisone every 3 weeks. Adverse events (AEs) were reported using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. Despite the advanced stage of disease and frailty of our study population, there were no unexpected side effects. The most common AEs were hematologic. Neutropenia was observed in nine (40.9%) patients and of grade≥3 in six (27.2%). No febrile neutropenia occurred. The most common nonhematologic AEs were diarrhea and asthenia, reported in eight (36.3%) and in five (22.7%) patients, respectively. In this setting, Cbz toxicity seems to be manageable and comparable with second-line Cbz. Therefore, our results seem to support the safety of Cbz as a third-line treatment for mCRPC patients.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

The primary objective of this study was to determine the activity and safety of 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine in the first-line treatment of advanced biliary tract cancer. Treatment consisted of intravenous oxaliplatin 100 mg/m every 3 weeks combined with intravenous gemcitabine 1000 mg/m on days 1 and 8 and oral capecitabine 1500 mg/m 14 days on 21 in two divided doses. Treatment was administered until progressive disease, unacceptable toxicity, or patient refusal. Thirty-seven patients were enrolled: eight patients had Eastern Cooperative Oncology Group 2 performance status at presentation. The overall response rate was 35.1% [95% confidence interval (CI): 20.2-52.5%] and the disease control rate was 72.9%. The median progression-free survival was 9.4 months (95% CI: 4.1-12.2 months) and the median overall survival was 13.8 months (95% CI: 7.7-17.1 months). There were no grade 4 toxicities. Grade 3 neutropenia occurred in 13.5% of patients and grade 3 thrombocytopenia in 10.8%. The present study suggests that 3-weekly oxaliplatin combined with gemcitabine and oral capecitabine is an active and well-tolerated chemotherapy regimen in the first-line treatment of metastatic biliary tract cancer.

Prostate cancer is the second leading cause of cancer-related death in men in most Western countries. In this report, we present 2 cases of metastatic castration-resistant prostate cancer and chronic kidney disease. Both patients underwent and developed clinical resistance to androgen-deprivation therapy. Subsequently, the patients were treated with the conventional chemotherapeutic approach, which resulted in the worsening of renal function and performance status. Therefore, we opted for treatment with abiraterone acetate, and the patients exhibited improvements in renal function with good response of the disease.

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.