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Purpose The aim of the present study was to test whether the coefficient of variation (CoV) of 18 F-FDG PET/CT images of metastatic lymph nodes and primary tumors may predict clinical outcome in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Fifty-eight NSCLC patients who had undergone 18 F-FDG PET/CT at diagnosis were evaluated. SUVmax, SUVmean, CoV, MTV and TLG were determined in targeted lymph nodes and corresponding primary tumors along with Total MTV (MTV TOT ) and Whole-Body TLG (TLG WB ) of all malignant lesions. Univariate analysis was performed using Cox proportional hazards regression whereas the Kaplan-Meier method and log-rank tests were used for survival analysis. Results Fifty-eight metastatic lymph nodes were analyzed and average values of SUVmax, SUVmean, CoV, MTV and TLG were 11.89 ± 8.54, 4.85 ± 1.90, 0.37 ± 0.16, 46.16 ± 99.59 mL and 256.84 ± 548.27 g, respectively, whereas in primary tumors they were 11.92 ± 6.21, 5.47 ± 2.34, 0.36 ± 0.14, 48.03 ± 64.45 mL and 285.21 ± 397.95 g, respectively. At univariate analysis, overall survival (OS) was predicted by SUVmax ( p = 0.0363), SUVmean ( p = 0.0200) and CoV ( p = 0.0139) of targeted lymph nodes as well as by CoV of primary tumors ( p = 0.0173), MTV TOT ( p = 0.0007), TLG WB ( p = 0.0129) and stage ( p = 0.0122). Using Kaplan-Meier analysis, OS was significantly better in patients with CoV of targeted lymph nodes ≤ 0.29 than those with CoV > 0.29 ( p = 0.0147), meanwhile patients with CoV of primary tumors > 0.38 had a better prognosis compared to those with CoV ≤ 0.38 ( p = 0.0137). Finally, we combined the CoV values of targeted lymph nodes and primary tumors in all possible arrangements and a statistically significant difference was found among the four survival curves ( p = 0.0133). In particular, patients with CoV of targeted lymph nodes ≤ 0.29 and CoV of primary tumors > 0.38 had the best prognosis. Conclusions The CoV of targeted lymph nodes combined with the CoV of primary tumors can predict prognosis of NSCLC patients.

We investigated the role of Coefficient of Variation (CoV), a first-order texture parameter derived from 18 F-FDG PET/CT, in the prognosis of Non-Small Cell Lung Cancer (NSCLC) patients. Eighty-four patients with advanced NSCLC who underwent 18 F-FDG PET/CT before therapy were retrospectively studied. SUVmax, SUVmean, CoV, total Metabolic Tumor Volume (MTV TOT ) and whole-body Total Lesion Glycolysis (TLG WB ) were determined by an automated contouring program (SUV threshold at 2.5). We analyzed 194 lesions: primary tumors ( n = 84), regional ( n = 48) and non-regional ( n = 17) lymph nodes and metastases in liver ( n = 9), bone ( n = 23) and other sites ( n = 13); average CoVs were 0.36 ± 0.13, 0.36 ± 0.14, 0.42 ± 0.18, 0.30 ± 0.14, 0.37 ± 0.17, 0.34 ± 0.13, respectively. No significant differences were found between the CoV values among the different lesion categories. Survival analysis included age, gender, histology, stage, MTV TOT , TLG WB and imaging parameters derived from primary tumors. At univariate analysis, CoV ( p = 0.0184), MTV TOT ( p = 0.0050), TLG WB ( p = 0.0108) and stage ( p = 0.0041) predicted Overall Survival (OS). At multivariate analysis, age, CoV, MTV TOT and stage were retained in the model ( p = 0.0001). Patients with CoV > 0.38 had significantly better OS than those with CoV ≤ 0.38 ( p = 0.0143). Patients with MTV TOT ≤ 89.5 mL had higher OS than those with MTV TOT > 89.5 mL ( p = 0.0063). Combining CoV and MTV TOT , patients with CoV ≤ 0.38 and MTV TOT > 89.5 mL had the worst prognosis. CoV, by reflecting the heterogeneity of glycolytic phenotype, can predict clinical outcomes in NSCLC patients.

Background: The DIO2 Thr92Ala polymorphism (rs225014), which occurs in about 15-30% of Caucasian people, determines a less efficient type 2 deiodinase (D2) enzyme. The aim of this study was to determine the impact of DIO2 Thr92Ala polymorphism on the serum thyrotropin (TSH) levels in thyroidectomized patients with hypothyroidism and to evaluate whether TSH levels and aging could be related, at pituitary level, to D2 activity. Methods: This prospective study was performed on 145 thyroid cancer patients, treated with total thyroidectomy, and undergoing radioiodine treatment after 3 weeks of levothyroxine (LT4) withdrawal. A mouse model has been used to determine D2 protein and mRNA levels in pituitary during aging. Results: Genetic analysis identified DIO2 Thr92Ala polymorphism in 56% of participants: 64/145 (44%) patients were homozygous wild type (WT) (Thr/Thr), 64 (44%) heterozygous (Thr/Ala), and 17 (12%) homozygous mutant (Ala/Ala). A significant negative relationship was observed between aging and the rise in serum TSH levels during LT4 withdrawal. However, this negative correlation found in WT was reduced in heterozygous and lost in mutant homozygous patients (Thr/Thr r  = -0.45, p  = 0.0002, 95% confidence interval [CI] -0.63 to -0.23; Ala/Thr r  = -0.39, p  = 0.0012, CI -0.60 to -0.67; and Ala/Ala r  = -0.30, p  = 0.2347; CI -0.70 to 0.20). Accordingly, when we compared the TSH measured in each patient to its theoretical value predicted from age, the TSH did not reach its putative target in 47% of WT patients, in 70% of Ala/Thr, and 76% of Ala/Ala carrying patients ( p  = 0.0036). This difference was lost in individuals older than 60 years, suggesting a decline of D2 associated with aging. The hypothesis that the pituitary D2 decreases with age was confirmed by the evidence that D2 mRNA and protein levels were lower in pituitary from old versus young mice. Conclusion: An age-related decline in TSH production in response to hypothyroidism was correlated with decreased D2 levels in pituitary. The presence of DIO 2 homozygous Ala/Ala polymorphism was associated with a reduced level of TSH secretion in response to hypothyroidism, indicating a decreased pituitary sensitivity to serum thyroxine variation (Institutional Research Ethics board approval number no. 433/21).

Objective: The aim of this study was to investigate the incidence of stoma recurrence and the therapeutic strategy outcomes in relation to survival that have been adopted over the past few decades using a monoclonal antibody, specifically nivolumab., Methods: This study included a total of 487 patients diagnosed with laryngeal carcinoma undergoing either a laryngectomy or salvage surgery after conservative interventions at the ENT Unit of Federico II University in Naples, Italy, between 2011 and 2021. Following a minimum 2.5-year follow-up and a maximum 21-year follow-up, the results revealed that only 38 patients suffered a stomal recurrence., Results: Despite various adopted treatment strategies, the literature reports lower patient survival rates. Following a total laryngectomy, stomal recurrence represents a therapeutic management challenge due to a poor prognosis for nearly every treated case. According to the literature, in fact, despite a low incidence (ie, 0.8-31.3%), the overall mortality rate increases from 77% to 100% after three years. Nevertheless, introducing immunotherapy into cancer treatment has resulted in an observable revolution in the treatment of different types of cancers over the years., Conclusion: In light of recorded data on survival following the use of the nivolumab, the case presented in this study allows a new perspective of successfully treating recurrences of squamous carcinoma of the head and neck., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest concerning this article’s research, authorship, and/or publication.

Aims: As the world population grows older, the co-existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio-Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications., Methods and Results: We enrolled 231 consecutive patients referred to our Cardio-Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48 month-survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow-up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P = 0.04)., Conclusions: Patients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Uveal melanoma is the most common primary intraocular malignancy. The aim of this retrospective study was to report the results after ruthenium-106 (Ru-106) plaque brachytherapy for uveal melanoma in terms of tumor control, visual acuity, radiation-related complications, tumor recurrence, metastases, and patients' survival rate during 4 years' follow-up. A total of 355 eyes from 355 patients have been treated with Ru-106 plaque brachytherapy for uveal melanoma between February 2011 and March 2020. Five patients were lost to follow-up, and then 350 eyes of 350 patients (mean age 58 ± 11 years) were enrolled in this retrospective study. All patients underwent a complete ophthalmic examination including echography and spectral domain-optical coherence tomography. The mean follow-up was 4 years (3 months to 9 years). After treatment, the mean tumor thickness was reduced to 1.75 ± 0.21 mm. Radiation complications were found in 63% of patients: 38% showed radiation maculopathy, 11% had optic neuropathy, and 14% developed cataracts. Cancer-free survival was 99%, 97%, and 85%, respectively, at 5, 7, and 9 years. Ru-106 plaque brachytherapy represents a reliable treatment of uveal melanoma. This technique is valid and safe with a low rate of ocular complications during a long-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cennamo, Montorio, D’ Andrea, Farella, Matano, Giuliano, Liuzzi, Breve, De Placido and Cennamo.)

Purpose: To compare the impact of COVID-19 pandemic on 2-[ 18 F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy., Methods: We retrospectively reviewed the numbers and results of 2-[ 18 F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves: 1) February 3-April 30, 2020; 2) October 15, 2020-January 15, 2021; and 3) January 18-April 16, 2021., Results: A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 ± 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p = 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab., Conclusion: Despite the restrictive medical measures for the emergency, the number of 2-[ 18 F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Anaplastic thyroid cancer (ATC) is a rare but aggressive thyroid cancer, responsible for about 50% of all thyroid cancer-related deaths. During the last two decades, the development of a multimodal personalized approach resulted in an increased survival. Here, we present an unusual case of a 54-year old woman with a paucicellular metastatic ATC, a rare variant of ATC, who was treated with a combination of surgery, radiation therapy and cytotoxic chemotherapy. More than two years later, when the disease was rapidly growing, a combination of lenvatinib and pembrolizumab induced a partial tumor response of lung metastasis that persisted over 18 months. Paucicellular ATC may initially show a less aggressive behavior compared to other histological ATC variants. However, over the time, its clinical course can rapidly progress like common ATC. The combination of lenvatinib and pembrolizumab was effective as a salvage therapy for a long period of time.

Background and Purpose: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that enhance the immune response against cancer cells. ICIs are generally well tolerated, although endocrine immune-related adverse events (irAEs) are common. We investigated the risk factors for thyroid irAEs in patients treated with ICIs. Moreover, we evaluated the clinical outcome of subjects who became hypothyroid compared to euthyroid patients., Patients and Methods: We retrospectively analyzed a series of 195 consecutively subjects treated with ICIs for metastatic tumors at the University of Naples "Federico II" between January 2014 and March 2020. Only subjects tested for thyroid function before and during the treatment with ICIs were included., Results: In the 96 patients treated with ICIs who were included [66 males, median age: 62 years (27-87)], thyroid irAEs occurred in 36 (37.5%), 16 (16.7%) a transient thyrotoxicosis, and 20 (20.8%) an hypothyroidism (in nine subjects hypothyroidism was preceded by a transient thyrotoxicosis). Only baseline TSH levels above 1.67 mIU/L and positive anti-thyroid antibodies (Ab-T) were associated with a higher risk of hypothyroidism. Patients with hypothyroidism during ICI treatment showed an improved 2-year PFS (HR = 0.82 CI 0.47-1.43; p = 0.0132) and OS (HR = 0.38 CI 95% 0.17-0.80; p = 0.011) compared to euthyroid patients., Conclusions: Baseline TSH levels above 1.67 mIU/L and presence of Ab-T are risk factors for the development of thyroid irAEs. Patients affected by thyroid irAEs showed a longer survival than patients who remained euthyroid., (© 2021. The Author(s).)

Recently, newer therapies such as immunotherapy have been increasingly used in the treatment of several tumors, including advanced melanoma. In particular, several studies showed that the combination of ipilimumab, an anti-Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) monoclonal antibody and nivolumab, an anti-Programmed Death 1 (PD-1) monoclonal antibody, leads to improved survival in patients with metastatic melanoma. Despite that, immunotherapeutic agents may not reach therapeutic concentration in the brain due to the blood-brain barrier. We report the case of a 50-year-old man with advanced melanoma who underwent whole-body 18F-FDG-PET/CT before and after treatment with immunotherapy showing resistant brain metastases confirmed by subsequent MRI of the brain. Moreover, 18F-FDG-PET/CT was able to detect an immune-related adverse event such as enterocolitis that contributed to the worsening of patient conditions. This case shows how a whole-body methodology such as 18F-FDG-PET/CT can be useful in identifying melanoma cancer patients unresponsive to immunotherapy that may benefit from traditional palliative therapy in the effort to improve their quality of life.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are imaging parameters derived from 18F-FDG PET/CT that have been proposed for risk stratification of cancer patients. The aim of our study was to test whether these whole-body volumetric imaging parameters may predict outcome in patients with non-small cell lung cancer (NSCLC)., Methods: Sixty-five patients (45 men, 20 women; mean age ± SD, 65 ± 12 years), with histologically proven NSCLC who had undergone 18F-FDG PET/CT scan before any therapy, were included in the study. Imaging parameters including SUV max , SUV mean , total MTV (MTV TOT ) and whole-body TLG (TLG WB ) were determined. Univariate and multivariate analyses of clinical and imaging variables were performed using Cox proportional hazards regression. Survival analysis was performed using Kaplan-Meier method and log-rank tests., Results: A total of 298 lesions were analyzed including 65 primary tumors, 114 metastatic lymph nodes and 119 distant metastases. MTV TOT and TLG WB could be determined in 276 lesions. Mean value of MTV TOT was 81.83 ml ± 14.63 ml (SE) whereas mean value of TLG WB was 459.88 g ± 77.02 g (SE). Univariate analysis showed that, among the variables tested, primary tumor diameter (p = 0.0470), MTV of primary tumor (p = 0.0299), stage (p < 0.0001), treatment (p < 0.0001), MTV TOT (p = 0.0003) and TLG WB (p = 0.0002) predicted progression-free survival in NSCLC patients, while age (p = 0.0550), MTV of primary tumor (p = 0.0375), stage (p < 0.0001), treatment (p < 0.0001), MTV TOT (p = 0.0001) and TLG WB (p = 0.0008) predicted overall survival. At multivariate analysis age, TLG WB and stage were retained in the model for prediction of progression-free survival (p < 0.0001), while age, MTV TOT and stage were retained in the model for prediction of overall survival (p < 0.0001). Survival analysis showed that patients with TLG WB  ≤ 54.7 g had a significantly prolonged progression-free survival as compared to patients with TLG WB  > 54.7 g (p < 0.0001). Moreover, overall survival was significantly better in patients showing a MTV TOT  ≤ 9.5 ml as compared to those having MTV TOT  > 9.5 ml (p < 0.0001). Similar results were obtained in a subgroup of 43 patients with advanced disease (stages III and IV)., Conclusions: Whole-body PET-based volumetric imaging parameters are able to predict outcome in NSCLC patients.

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in young-aged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m/day on days 1-5, vincristine 1,5 mg/m/day on days 1 and 5, and doxorubicin 60 mg/m/day on day 5; CVP: cisplatin 40 mg/m/day on days 1-5 and etoposide 100 mg/m/day on days 1-5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustine-teniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies.

Rationale: Paraneoplastic limbic encephalitis (PLE) is one of the most common causes of neurologic paraneoplastic syndromes, with unclear pathogenesis. While several reports published in the last decades showed the occurrence of PLE in a variety of cancers, only a few cases have been associated with colon cancer., Patient Concerns: In February 2017, a 54-year-old man with clinical history of radically resected colon cancer started first line chemotherapy with FOLFOXIRI plus bevacizumab, after radiological diagnosis of multiple liver and bone metastases. During the third cycle of treatment, the patient developed psychomotor agitation and hallucinations followed by severe consciousness level reduction and cognitive impairment., Diagnoses: Magnetic resonance imaging showed hyperintense signals in both hippocampal areas, insula and right cingulate gyrus on fluid attenuated inversion recovery, diffusion weighted imaging, and T2-weighted images, highly suggestive of limbic encephalitis. Other causes (brain metastases, toxicity of chemotherapeutic agents, and infections) were excluded., Interventions: Empirical immunosuppressive treatment (high-dose immunoglobulins and corticosteroids) was administered and chemotherapy was resumed., Outcomes: A slowly progressive improvement in neurological condition has been observed, even though radiological signs of limbic encephalitis are still evident., Lessons: The present case highlights the complex diagnostic process of PLE, and the lack of a standard treatment. Moreover, the absence of correlation between PLE and tumor progression or tumor burden, and the opportunity of treating underlying neoplasm is discussed.

Background: The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis., Materials and Methods: We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model., Results: The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p  = .001), 6 months (75.4% vs. 58.6%, p  < .001), and 12 months (69.8% vs. 58.3%, p  = .014)., Conclusion: ONKOTEV score steps into history of cancer-related-VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program. The Oncologist 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous thromboembolism in cancer outpatients with a risk model score will drive physicians' decision of starting thromboprophylaxis in high-risk patients., (© AlphaMed Press 2017.)

Background: Basaloid squamous cell carcinoma (BSCC) is a high-grade variant of squamous cell carcinoma usually localized in the aerodigestive tract, with a poor prognosis. Surgical resection is generally recommended, even if no standard treatment has been established yet., Case Report: Here, we report the case history of a patient diagnosed with BSCC at the esophagogastric junction who was successfully treated with chemotherapy alone, leading to a durable complete response., Conclusions: The presented case illustrates the diagnostic challenges associated with BSCC of the esophagus and reports an unexpected chemosensitivity of this histotype to the combination of a platinum salt plus 5-fluorouracil, which could represent an optimal treatment strategy in unfit patients., (© 2014 S. Karger GmbH, Freiburg.)

Pancreatic and biliary tract carcinomas are very chemoresistant. After a first-line treatment with a gemcitabine-based regimen, no second-line scheme is consolidated in clinical practice. The aim of this study was to evaluate the toxicity and the activity of the FOLFIRI regimen as first-line or second-line chemotherapy in patients with pancreatic or biliary tract tumors. Fifty-four patients (30 with pancreatic tumor, nine with gallbladder tumor, and 15 with biliary tract tumor) were treated with FOLFIRI (irinotecan 180 mg/m², day 1; leucovorin 100 mg/m² intravenously, days 1 and 2; 5-fluorouracil 400 mg/m² intravenous bolus, days 1 and 2; and 600 mg/m² in 22 h intravenously, continuous infusion days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the NCI-CTC V3.0 criteria, the response rate was verified each four cycles according to the RECIST criteria, and the progression-free survival rates as well as the overall survival rates were calculated according to the Kaplan-Meier method. Overall, the toxicity was mild. Grade 3-4 neutropenia occurred in 42.6% of patients. Grade 3-4 gastrointestinal toxicity was rare. FOLFIRI as a first-line treatment produced a response rate of 25%. In the second-line group, 9/21 patients (42.9%) obtained a stable disease as best response. In the entire population, the median progression-free survival rates were 3.1 months [95% confidence interval (CI), 1.9-4.4] and 3.5 months (95% CI, 2.6-4.4), respectively, in the first-line and the second-line cohort of patients. The median overall survival rates were 14.5 months (95% CI, 7.0-22.1) and 6.2 months (95% CI, 5.4-7.0), respectively, in the first-line and the second-line cohort of patients. FOLFIRI is feasible and well tolerated in patients with pancreatic or biliary tract tumors; it has a good activity in first line and mostly in patients with pancreatic cancer.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

Aim: To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS)., Methods: Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value < 0.05 was considered statistically significant, and all tests were two-sided., Results: Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133)., Conclusion: Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.

Background: Bladder involvement by a secondary tumor is fairly rare and an uncommon source of bladder metastasis is the stomach., Case Report: The authors report a case of a 38-year-old man with a bladder metastasis from a gastric signet-ring-cell (SRC) adenocarcinoma who presented with ematuria. The clinical history and the presence of SRCs in the voided urinary cytology and histologically in the suburothelial connective, with an overlying intact urothelium suggested a diagnosis of bladder metastasis from gastric carcinoma., Conclusion: Bladder involvement by a secondary tumor is very rare, and a SRC carcinoma metastatic to the bladder, albeit extremely rare, should be considered in the differential diagnosis.

Intracranial malignancies can be complicated by seizure activity, and anticonvulsants such as phenytoin are usually administered to prevent this neurological kind of complication. Cranial radiation therapy is instead the treatment of choice when the tumor is unresectable. Anyway, the combination of phenytoin and cranial radiation therapy can lead to a rare and severe mucocutaneous complication called EMPACT syndrome. It is composed of "erythema (E) multiforme (M) associated with phenytoin (P) and (A) cranial radiation (C) therapy (T)." Herein, we report 2 cases of EMPACT syndrome related to the use of phenobarbital instead of phenytoin as usually described in literature.

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel-cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.

Background: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G)., Methods: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets., Results: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens., Conclusions: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

Purpose: Thymic epithelial tumors (TETs) are rare tumors of the mediastinum, with an estimated incidence of about 3 cases per 100,000 inhabitants. Although anthracycline- and platinum-based chemotherapy is an active treatment for TETs, novel systemic therapeutic options are especially needed for metastatic disease, which is virtually incurable. On the basis of the radiographic response obtained with imatinib (Novartis Pharma, Basel, Switzerland) in a patient with thymic carcinoma harboring the V560del c-KIT mutation, a phase II trial was initiated at the Department of Molecular and Clinical Oncology and Endocrinology of University "Federico II of Naples" with the purpose to test imatinib in TETs., Methods: Imatinib was daily delivered at the dose of 400 mg to patients affected by TETs, who had progressed after at least one chemotherapy regimen. Positivity of c-KIT on immunohistochemistry was not mandatory for study entry. Radiographic responses were measured by CT scans performed every 3 months, according to the RECIST criteria. Toxicity was graded according to the Common Toxicity Criteria of the National Cancer Institute, version 3.0., Results: Fifteen patients with advanced TETs were enrolled from March 2008 to May 2010. Three patients presented with thymic carcinomas. Two of these three patients presented c-kit expression on immunohistochemistry. No patient harbored a known c-kit activating mutation. Imatinib was very well tolerated, with no toxicity-related death. Diarrhea and migraine were the most frequent events, occurring both in 20% of patients, but were manageable and mild. No radiographic responses were recorded. Median progression-free survival was 3 months (interquartile range, 2.5-4). Median overall survival was not reached. The study was terminated before it reached its target accrual of 42 patients, because of the lack of responses and low accrual rate., Conclusions: This trial indicates the lack of effectiveness of imatinib in unselected patients with thymic epithelial tumors. Nevertheless, imatinib may represent a valuable option in selected patients with TETs, such as those harboring the V560del c-KIT mutation.

Background: Previously published preliminary findings showed promising activity of paclitaxel in chemotherapy-pretreated metastatic penile cancer., Objective: To evaluate the activity and safety of paclitaxel in pretreated metastatic penile cancer., Design, Setting, and Participants: Twenty-five patients were enrolled in a single-arm phase 2 multicentre study and treated with 175 mg/m² paclitaxel at 3-wk intervals until disease progression or irreversible toxicity., Measurements: The objective response rate was the primary end point. Safety, progression-free survival (PFS), and overall survival (OS) were secondary end points., Results and Limitations: Partial responses were observed in 20% (5 of 25 patients). Grade 1-2 neutropenia, nausea, and oral mucositis were the most common side effects, noted in 13, 9, and 8 patients, respectively. Grade 3-4 neutropenia was reported in seven patients (28%). Median PFS was 11 wk (95% confidence interval [CI], 7-30); median OS was 23 wk (95% CI, 13-48). Median survival in responders was 32 wk (95% CI, 20-48). One limitation of our study was the limited accrual, which did not reach the target of 27 patients, due to the typical slow enrolment of a rare disease., Conclusions: Final results of this study demonstrate that paclitaxel is moderately active and well tolerated. Further trials, which may also explore the combination of paclitaxel with other agents, are required to confirm our findings., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The combination of EGFR inhibitors and anti-angiogenic drugs has a strong pre-clinical rationale, yet its use has produced controversial clinical results. We conducted two sequential phase I trials to evaluate the feasibility and the recommended dose of erlotinib when combined with fluoropyrimidine-oxaliplatin-based chemotherapy with or without bevacizumab. A total of 21 metastatic colorectal cancer (mCRC) patients were treated in two sequential phase I trials. In the first trial, 12 patients were treated with escalating doses of erlotinib plus FOLFOX. In the second, 9 patients were treated with escalating doses of erlotinib combined with oxaliplatin, capecitabine and bevacizumab. No MTD was reached in either of the trials. The only dose-limiting toxicities observed were neutropenia and diarrhea. No unexpected toxicities were noted. Hematological toxicity was the most frequently noted adverse event with infusional 5FU therapy, while gastrointestinal toxicity was the most common adverse event. In the second trial most patients withdrew from treatment due to toxicity, and less than half completed the therapeutic program as per protocol, mostly due to toxicity. In conclusion, the present study confirms the disappointing results of the double combination of EGFR inhibitors and anti-angiogenic drugs in mCRC patients.

The aim of the present study was to evaluate the toxicity and efficacy of the FOLFOX-4 regimen as adjuvant chemotherapy in patients with gastric cancer after radical surgery. Fifty-four patients (1 stage Ib, 6 stage II, 22 stage IIIa, 14 stage IIIb and 11 stage IV) received 8-12 cycles of FOLFOX-4 (oxaliplatin 85 mg/m(2), Day 1; leucovorin 100 mg/m(2) i.v., Days 1 and 2; 5-fluorouracil 400 mg/m(2) i.v. bolus, Days 1 and 2 and 600 mg/m(2) in 22 h i.v. continuous infusion, Days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the National Cancer Institute Common Toxicity Criteria. Disease-free (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Thirty-eight patients (70.4%) completed the prescribed number of cycles of chemotherapy. The toxicity was mild. Grade 3-4 neutropenia occurred in 57% of patients, thrombocytopenia and anemia in 2% of cases. Peripheral neuropathy was experienced by 46% of the patients (grade 4 in 2% of cases). Five patients experienced grade 3 gastrointestinal toxicity. After a median follow-up of 33.1 months, 17 patients relapsed and 17 succumbed to the disease. The mean observed DFS and OS were 49.7 months (range 40.7-58.8) and 57.9 months (range 49.6-66.2), respectively. At univariate analysis, females and patients who had received <8 cycles of chemotherapy had a significantly worse probability of DFS and OS. The Cox model showed gender to be independent of the factors affecting DFS. Adjuvant FOLFOX-4 is feasible and well-tolerated in patients radically resected for gastric cancer. Receiving <4 months of adjuvant FOLFOX-4 could be detrimental to prognosis.

Aim: To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma (DLBCL)., Methods: Sixty patients (median age: 58 years) with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007, were included in this analysis. Patients were selected by stage (I-IV, Lugano staging system), European Cooperative Oncology Group performance status (0-2) and treatment strategies. Treatment strategies were chemotherapy alone (group A, n = 30) [scheduled as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and CHOP-like], and chemotherapy combined with rituximab (group B, n = 30). The primary end point of the study was complete response (CR) rate; the secondary end points were disease-free survival (DFS) at 5 years and overall survival (OS)., Results: Median follow-up was 62 mo (range: 31-102 mo). We observed a significant difference between the two groups (A vs B) in terms of CR [76.6% (23/30) vs 100%, P = 0.04) and DFS at 5 years [73.3% (22/30) vs 100%, P = 0.03). To date, 19 group A (63.3%) patients are alive and 11 have died, while all group B patients are alive. No significant differences in toxicity were observed between the two groups., Conclusion: Rituximab in combination with chemotherapy improves CR rate, DFS and OS. Further prospective trials are needed to confirm our results.

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

Purpose: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm)., Results: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05)., Conclusion: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

Background: Chronic subcutaneous rIL-2 at low doses produces long-lasting immunomodulatory effects and is considered an effective treatment for renal cell carcinoma with marginal activity in malignant melanoma and colorectal cancer., Patients and Methods: In this study we evaluated, by Minnesota Multiphasic Personality Inventory (MMPI), the psychological changes induced by rIL-2 in 10 patients with advanced tumors., Results: After 3 months of rIL-2 treatment, 80% of the patients had a significantly increased score on the clinical scale of depression (D) and psychasthenia (Pt) (p<0.01), 70% on the scale of conversion hysteria (Hy) and 60% on the scales of schizophrenia (Sc) and psychopathic deviate (Pd), (p<0.05). These MMPI changes were however not paralleled by disease progression or clinical-overt psychological disease., Conclusion: These findings demonstrate that low-dose rIL-2 is a psychoactive treatment, which deserves psychological monitoring The MMPI is feasible for the evaluation of subclinical psychological modifications induced by cytokine immunotherapy.

Background: DNA damage caused by platinum agents is frequently followed by induction of topoisomerase I, providing a rationale for use of platinum-based compounds with topoisomerase I inhibitors., Materials and Methods: We studied the effect of a sequential schedule of oxaliplatin on day I and topotecan on days 2-5, in human colon and ovarian cancer cells in vitro, in nude mice bearing human cancer xenografts and finally in cancer patients in a phase I trial., Results: We demonstrated a supra-additive effect of this combination on inhibition of colony formation and induction of apoptosis in vitro. We then demonstrated that the two agents in combination markedly inhibit tumor growth in nude mice. We translated these results into a clinical setting, conducting a phase I study in cancer patients with oxaliplatin 85 mg/m2 on day 1 and topotecan at doses escalating from 0.5 to 1.5 mg/m2 on days 2-5. Sixty cycles of treatment were administered to 18 patients affected prevalently by ovarian and colorectal cancer. Combination with topotecan 1.5 mg/m2 caused a dose-limiting toxicity. Therefore the maximum tolerated dose of topotecan was 1.25 mg/m2, at which six patients experienced a mild hematological and gastrointestinal toxicity. We also obtained evidence of clinical activity, particularly in ovarian cancer., Conclusions: Our results provide a solid biological and clinical rationale for a phase II trial at the recommended doses of oxaliplatin 85 mg/m2 and topotecan 1.25 mg/m2, possibly in ovarian cancer patients.

Gemcitabine and 5-fluorouracil are the only two compounds with reproducible activity against advanced pancreatic cancer (APC). We have evaluated a novel combination of gemcitabine and 5-fluorouracil on the clinical benefit response (CBR) end point. Eleven consecutive patients with symptomatic APC were entered in a two-stage phase II trial. Gemcitabine was administered by intravenous (i.v.) bolus injection at the dose of 1,000 mg m(-2) on days 1, 8, 15 and 5-fluorouracil 500 mg m(-2) was given by continuous i.v. infusion on days 1-5. Treatment was repeated every 28 days. A CBR was achieved in 7/11 patients. The mean time to loss of CBR was 26.5 weeks (range 14-18, median 22). Toxicity was mild and no APC patient experienced WHO grade 3 toxicity. The gemcitabine/5-fluorouracil combination is well tolerated and produces a symptomatic relief in the majority of APC patients.

Aim of the study was to improve cure rate and survival of aggressive non-Hodgkin's lymphoma (NHL) with a tailored program of therapy based on histologic type, prognostic characteristics of patients and response to therapy, and with the use of differentiating or cytostatic agents such as Ara-C at low doses and alphaIFN. Fifty-four consecutive patients with aggressive NHL were treated in the induction phase with 4 sequential courses of a third generation regimen (modified CODBLAM IV), followed in responsive patients by 1 cycle of doxorubicin and cyclophosphamide and 1 cycle of high dose methotrexate with folinic acid rescue (AC-MTX). Patients who achieved partial response (PR) were treated with the combination of CCNU + vinblastine if affected by high grade NHL, or with low dose Ara-C plus alphaIFN if affected by intermediate grade NHL. Patients who obtained complete response (CR) with basal adverse prognostic factors were treated with alphaIFN as maintenance therapy for two years. Radiotherapy and surgery were effected in selected cases. Thirty-four patients (62.9%) achieved CR and 12 patients (22.2%) showed PR after induction therapy. Among the 12 patients who achieved PR, 6 prolonged CRs were obtained in 7 patients treated with Ara-C at low doses plus alphaIFN and 4 CRs were obtained in 5 patients treated with CCNU + vinblastine. After completion of treatment, 44 patients (81.5%) obtained CR, 2 patients (3.7%) showed PR and 8 patients (14.8%) presented progression of disease (PD). Fifteen patients received alphaIFN as maintenance therapy. The overall survival and failure-free survival rates are 53.7% and 50% respectively, with a median follow-up of 82 months: 27 patients remain alive, disease-free without relapses, and can be considered cured. This tailored program of therapy resulted effective and moderately toxic and may improve the outcome in aggressive NHL.

A phase II clinical trial of subcutaneous recombinant Interleukin 2 (rIL-2) given by 5 days pulses followed by a 9 days rest has been performed in patients affected by renal cell carcinoma, malignant melanoma and colorectal cancer. A total of 25 patients entered the study, completed at least six courses of treatment, and were evaluable for toxicity and response to treatment. This schedule of subcutaneous rIL-2 was well tolerated and no World Health Organization grade 3 side effects were observed. A 33.3% response rate was recorded in patients affected by renal cell carcinoma, although no major responses were achieved in patients with malignant melanoma and colorectal cancer. A durable increase of natural killer activity retained by poeripheral blood mononuclear cells was demonstrated in these patients and was paralleled by increased serum levels of interferon gamma and tumor necrosis factor a without changes of circulating interleukin-1d. It is concluded that this schedule of pulse administration of subcutaneous rIL-2 has antitumor activity in renal cell carcinoma and produces durable biomodulatory effects.

We have demonstrated that interferon-alpha 2 recombinant (IFN alpha) inhibits the growth and modulates the expression of the receptor for transferrin (TRF-R) in human epidermoid carcinoma KB cells. Receptor upregulation results in the reconstitution of intracellular iron levels in the IFN alpha-treated cells. Several anti-TRF-R murine monoclonal antibodies (MAbs) have been generated which induce tumor cell growth inhibition through blockade of receptor function. We have evaluated by MTT assay the effect of anti-TRF-R 42/6, E2.3, A27.15 and D65.30 MAbs given in combination with IFN alpha on the growth of human epidermoid carcinoma KB cells. We found that IFN alpha and A27.15 MAb induced a synergistic antiproliferative effect on these cells. These results suggest that IFN alpha may potentiate the antitumor efficacy of TRF-R-targeted therapy.

The antitumor activity and toxicity profile of a new therapeutic combination was investigated for patients with non-Hodgkin's lymphoma (NHL). The regimen consisted of mitoxantrone (10 mg/m(2)/day by intravenous (i.v.) bolus injection on day 1), etoposide (100 mg by 24 hours continuous i.v. infusion on days 1, 2, 3) and bleomycin (4 mg by i.v. bolus injection on day 1 followed by 24 hours continuous i.v. infusion at 4 mg/m2/day dose on days 1, 2, 3) (MEB). MEB chemotherapy was administered to 22 patients affected by intermediate/high grade or clinically symptomatic low grade NHL who were considered non-elegible for standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. Major responses were achieved in 11/22 (50%) patients with 5 (23%) complete responses. Grade 3-4 neutropenia occurred in 59% of patients. The results of this study demonstrate that MEB chemotherapy possesses good antitumor activity and a manageable toxicity in a prognostically unfavourable subset of lymphoma patients.

Forty-five patients with stage III-IV low grade non-Hodgkin's lymphoma (NHL) were treated with a non-intensive polychemotherapy regimen including chlorambucil-vincristine and cytarabine (Ara-C), termed COA, for a total of 366 courses, beginning in June 1986. Grade 4 myelotoxicity occurred in only 4/45 patients. No treatment related death was observed. All patients were evaluable for response. Overall, 38 (84%) objective responses, including 31 (69%) complete responses (CR), were observed. At a median follow-up of 57 (21-84+) months, only 8 deaths occurred. Twenty-seven (60%) patients are still disease-free. All disease-free patients were in their first CR. The seven-year estimated survival is 71% and the estimated 7-year progression-free survival (PFS) was 48%. The estimated probability of complete responders to be disease-free at 6 years is 78%. Pretreatment laboratory parameters (serum levels of thymidine kinase, LDH and TNF-alpha showed a good prognostic relevance at using univariate analysis. At multivariate analysis, only the pretreatment serum levels of TNF-alpha were significantly associated with a higher CR achievement probability (p = 0.02) and a longer PFS (p = 0.02). We established a risk model for clinical outcome based on these 3 parameters. Patients having all parameters within the normal range at diagnosis, showed a very good prognosis (100% 7-year PFS and survival), while patients with all parameters increased had a very poor prognosis (0% 7-year PFS and 22% 7-year survival). In conclusion, COA treatment appears to be a non-toxic and very effective treatment for low-grade non-Hodgkin's lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

High dose Verapamil (VP) infusion has been incorporated into cytotoxic chemotherapy in order to circumvent tumor cell drug-resistance. We have evaluated the cardiovascular side-effects produced by high dose VP associated to EPOCH chemotherapy in 12 patients with chemorefractory lymphoma. Continuous monitoring of right ventricular and pulmonary pressure and cardiac index was performed in three patients by a Swan-Ganz catheter. A slight reduction in cardiac index was observed 6 h after the beginning of VP infusion and was followed by spontaneous recovery within 12 h. First degree atrioventricular (AV) block was detected in 6/12 patients. Premature Ventricular Beats (PVB) occurred in one patient, and promptly disappeared after xylocaine administration. All patients experienced mild and transient hypotension, while severe hypotension was observed only in 1 patient, who promptly recovered when VP administration was discontinued. Hypokalemia was detected in 6 patients possibly as a consequence of transient activation of the renin-angiotensin system.