Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Acute infusion reactions to chemotherapeutic drugs: a single institute experience.

PURPOSE: Treating cancer often involves the use of chemotherapeutic agents. Due to the growing incidence of cancer worldwide and the expanding number of treatment options, it is important to understand the risks of adverse events associated with these treatments. In this study, we monitored the occurrence of acute infusion reactions in an outpatient chemotherapy center from April 2011 to April 2012. METHODS: For patients who developed infusion reactions, the causative drug, the dose and number of treatments received, the onset time of the reaction, the duration of the reaction, blood pressure, pulse, level of oxygen saturation during the reaction, and other symptoms were recorded. The severity of reactions was determined in accordance with NCI toxicity criteria. A reaction was considered as grade 1-2 (mild-moderate) if the patient experienced flushing, rash, fever, tremor, dyspnea, rigor, and mild hypotension. Symptoms such as severe hypotension, bronchospasm, cardiac dysfunction and anaphylaxis, requiring therapeutic intervention, were classified as severe, grade 3-4 reactions. RESULTS: Of the 2213 patients receiving chemotherapy during the study period, 138 (62%) developed an infusion reaction to the treatment. Among 138 patients most commonly treated types of carcinoma included breast (39.2%), lung (17.8%), colorectal (10%), and ovarian (8.5%) cancers. Docetaxel administration resulted in the largest number of infusion reactions, though most reactions were mild to moderate and did not require the cessation of treatment. Patients with mild to moderate reactions (89.2%) were able to continue treatment, while those who developed severe reactions (10.8%) could not continue treatment with the same agent. CONCLUSION: Although severe reactions are rare, the incidence of mild to moderate reactions against taxanes, platinum compounds, and monoclonal antibodies is quite high. Clinical symptoms do not vary widely among the agents, though the onset time of symptoms does vary. While reactions against platinum agents were of type 1 anaphylactic reactions, reactions against taxanes and monoclonal antibodies during the first infusion and in the following minutes suggest the activation of different mechanisms.

Capecitabine/cisplatin doublet in anthracycline and taxane pretreated and HER-2 negative metastatic breast carcinoma patients.

PURPOSE: To evaluate the activity and toxicity of the combination of capecitabine and cisplatin (CapCisp) in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma (MBC) female patients. METHODS: Patients with HER-2 negative MBC pretreated with anthracycline and taxane and who were then treated with CapCisp combination were retrospectively evaluated. All patients received Cap 1000 mg/m(2) on days 1-14, and Cisp 60 mg/m(2) on day 1, repeated every 3 weeks. In case of disease control without severe toxicity, single agent Cap was continued until progression or unacceptable toxicities after Cisp cessation. RESULTS: Sixty-four MBC patients with median age 43 years (range 20-66) were included the study. Infiltrative ductal carcinoma prevailed (85.9%). Ten percent of the patients had grade I, 42% grade II, and 48.0% grade III tumors. Estrogen receptor (ER) and progesterone receptor (PR) were positive in 48.4 and 51.6% of the patients, respectively. Twenty-eight percent of the patients had triple negative tumors. Almost the entire patient group had this regimen as a third-line treatment. The median combination chemotherapy cycles were 6 (range 2-8). Twenty-seven non-progressive patients continued treatment with single-agent Cap. Median single-agent Cap cycles after the combination chemotherapy were 4 (range 1-38). Disease control rate was 81.3% (complete response 6.3%; partial response 48.4%, stable disease 26.6%, progressive disease 18.8%). Median follow-up time was 10.6 months. Median time to disease progression was 7 months, median overall survival (OS) was 17 months (95% CI, 6.9-16.1) measured from the start of CapCisp chemotherapy. There were no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (8.1%), nausea - vomiting (7.8%) and thrombocytopenia (6.3%). CONCLUSION: CapCisp doublet has an encouraging antitumor activity with acceptable and manageable toxicity in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma patients.

It is not only the empty vials that go into the garbage can during chemotherapy drugs preparation: a cost analysis of unused chemotherapy drugs in cancer treatment.

PURPOSE: Cancer therapy is a costly treatment. Costs of drugs used in cancer therapy are gradually increasing with the addition of new and expensive drugs. This fact imposes obligation on reasonable drug usage. Occasionally, all of the prescribed drugs are not used for various reasons, and a number of drugs can be left over. In this study, we aimed to calculate the costs of unused chemotherapeutic drugs in our oncology clinics. METHODS: A total of 117 patients with 17 different types of cancer were administered 32 cancer therapy protocols during 2 months. After administration of ideal doses of the prescribed drugs calculated on an individual basis, the number of unused drug doses in the packages was recorded and the costs of the unused drugs were calculated based on current prices of the drugs. RESULTS: The cumulative cost of the unused drugs calculated for all patients was US dollars (USD) 6406.93, and average cost of the drug per capita was USD 54.76. Minimal and maximal unused drug costs per drug were USD 0.29 for 5-fluorouracil, and USD 247.12 for bevacizumab, respectively. Minimal increase in drug costs per recipe was USD 0.50 for a prescription containing cyclophosphamide and 5-fluorouracil, while the total cost of bevacizumab plus irinotecan combination increased tremendously to USD 309.12. Among chemotherapeutic protocols the cheapest one was AC (adriamycin, cyclophosphamide) with USD 4.77, while the most expensive one (USD 116.02) was FOLFIRI-B (5-fluorouracil, calcium folinate, irinotecan, and bevacizumab). CONCLUSION: The important financial burden of unused drugs goes unrecognized among routine chemotherapeutic applications. In order to be able to avoid this extravagance, drug industry, prescribing physicians, and practice nurses must assume important roles.

First-line therapy for metastatic colorectal carcinoma: modified FOLFOX4 or FOLFIRI-bevacizumab.

PURPOSE: The aim of this study was to compare the efficacy and toxicity of modified (m) FOLFOX4 (folinic acid, 5-fluorouracil [5-FU], and oxaliplatin) vs. FOLFIRI-B (folinic acid, 5-FU, irinotecan, and bevacizumab) as first-line treatment of metastatic colorectal carcinoma (MCRC). METHODS: The medical records of 89 MCRC patients treated with either mFOLFOX4 (group 1) or FOLFIRI-B (group 2) as first-line chemotherapy were evaluated retrospectively. RESULTS: Complete (CR) plus partial response (PR) were seen in 18 (36.7%) vs. 13 (32.5%) patients in the mFOLFOX4 vs. FOLFIRI-B, respectively (p=0.67). Median progression-free survival (PFS) was 9 months (95% CI 7.2- 9.5) vs. 10 months (95% CI 7.6-12.3) in group 1 vs. group 2, respectively (p=0.30). Median overall survival (OS) was 22 months (95% CI 17.6-26.3) and 19 months (95% CI 13-24.9) in group 1 and 2, respectively (p=0.32). There was no statistically significant difference in grade 3-4 hematological toxicity between the groups, but grade 3-4 grade weakness, diarrhea, nausea and vomiting was observed more frequently in the FOLFIRI-B patients (p=0.03, p=0.01, p=0.05, respectively). CONCLUSION: Our data suggest that mFOLFOX4 and FOLFIRI-B are equally effective as first-line chemotherapy in MCRC patients. This may partially be explained by the fact that almost 50% of those receiving FOLFOX in the first-line received FOLFIRI-B in the second-gline, an observation suggesting that bevacizumab in the second line may be as effective as in the first line.

Safety and efficacy of FOLFIRI-bevacizumab for metastatic colorectal carcinoma as second line treatment.

PURPOSE: To evaluate the efficacy and the safety of FOLFIRI-bevacizumab (B) in the 2nd line therapy of metastatic colorectal carcinoma (MCRC). METHODS: Between March 2006 and July 2009 35 patients with MCRC were treated with 2nd line therapy FOLFIRI- B (irinotecan 180 mg/m(2) D1, folinic acid 200 mg/m(2) D1, 5-fluorouracil/5 FU 400 mg/m(2) bolus D1, followed by 5 FU 2600 mg/m(2) 46-h continuous infusion, and bevacizumab 5 mg/kg D1, every 2 weeks) Their data were collected and analysed. RESULTS: The patient median age was 54 years (range 36-75). One patient (2.8%) had received oxaliplatin-based adjuvant chemotherapy and 33 patients (94.3%) were exposed to oxaliplatin during first line chemotherapy for MCRC. The median follow up period was 12.2 months (range 1.5-37.9). Complete remission (CR) was achieved in 5.7% of the patients and the sum of CR and partial remission (PR) was 11.4%. Disease control (CR+PR+stable disease/SD) was registered in 74.3% of the patients. During follow up, progression (PD) was seen in 32 (91.4%) patients and 23 (65.7%) patients had died. The median progression free survival (PFS) was 7.4 months (95%CI 5.5-9.3) and the median overall survival (OS) 13 months (95%CI 8.8-17.2). Grade 3-4 toxicity requiring delay of chemotherapy was observed in 12 (34.3%) patients with 10 patients (28.6%) having neutropenia and 2 (5.7%) diarrhea. CONCLUSION: FOLFIRI-B may be an efficient and safe choice in the 2nd line treatment of patients with MCRC previously treated with oxaliplatin.

Patients with advanced cholangiocarcinoma benefit from chemotherapy if they are fit to receive it: single center experience.

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients suffering from advanced cholangiocarcinoma (CCA). METHODS: The medical records of 93 patients with unresectable or metastatic CCA were retrospectively analyzed. RESULTS: Out of 93 patients, 53 (64.9%) were initially managed with palliative biliary drainage (PBD). Cisplatinbased regimens were administered to 18 (19.3%) patients, and non-cisplatin regimens (mainly 5-fluorouracil [5-FU]- based) were administered to 23 (24.8%) patients. Of all 93 patients 53 (55.9%) did not receive chemotherapy. The median overall survival (OS) for all patients was 6.1 months and was significantly higher in patients treated with chemotherapy as compared to those without chemotherapy (p=0.002). However, no difference in OS was seen in patients treated with cisplatin- or 5-FU-based chemotherapy. We noticed that a high number of patients were not referred to a medical oncologist even for advice. CONCLUSION: The relief of bile duct obstruction is an important part of the initial patient management. One of the main observations of this study was that systemic chemotherapy significantly improved survival. Increased awareness of the medical oncologists' role in the management of CCA can increase the number of patients who can have access to chemotherapy.

Frequency of comorbid illnesses in cancer patients in Turkey.

PURPOSE: Comorbidities in cancer patients can adversely affect the management and outcome of their primary illnesses at all levels from diagnosis to therapy. We sought to examine comorbid conditions of cancer patients, treated at 4 university hospitals, each representing a different geographic location in Turkey. METHODS: A total of 769 consecutive cancer patients presenting to outpatient clinics were recruited between November 2007 and May 2008. The patients filled in a questionnaire on comorbidities. Based on the questionnaire, Charlson Comorbidity Index (CCI( was calculated. RESULTS: The patient median age was 55 years (range 21-87) and 456 (59.3%) were female. Breast (36.5%), colorectal (21.4%) and lung cancers (13.9%) were the 3 most frequent malignancies. Of the patients, 59.3% had at least one comorbid disease and 46.3% were using at least one medication daily. The most frequent comorbidities were hypertension (25.3%), diabetes mellitus (13.1%) and peptic ulcer (7.7%). Increasing age positively correlated with the extent of comorbidities (r=0.30, p<0.001), number of medications (r=0.32, p<0.001) and the CCI (r=0.20, p<0.001). CONCLUSION: It is crucial to remember that comorbid illnesses are not rare and many patients are treated for conditions unrelated to their cancer, which potentially may affect various stages of their clinical management.

Socio-demographic parameters in screening for breast cancer: Lessons from a population-'based women's Health Project held in a province in Turkey.

PURPOSE: to inform healthy women about breast cancer and screen them, as well as to look for any relationship between demographic and clinical findings and breast cancer. METHODS: thirty-five health teams were created prior to the study. The teams were primarily trained for breast examination and for screening methods to detect breast cancer. RESULTS: a total of 77,934 subjects were evaluated. Clinical breast examination (CBE) was performed in 66% (n=51,706) of the participants. The characteristics of the subjects in the examined group were similar to those in the group refusing examination. The percentage of the subjects who declined examination was 2-fold higher in the ≥ 60 year age group compared to younger women. A breast mass was detected in 2,838 (6%) subjects who had undergone breast examination. Lower educational level and urban dwellers showed higher incidence of suspicious mass in CBE. Fifty-eight women were diagnosed with breast cancer. The cumulative incidence of breast cancer was 7.5/10.000 for all of the study population and 10.1/10.000 for women with CBE. CONCLUSION: elderly subjects, those living in rural areas and women with low educational and lower socio-economic levels should be convinced to undergo screening for breast cancer.

Posterior leukoencephalopathy after combination chemotherapy in a patient with lymphoma.

Posterior leukoencephalopathy syndrome is a recently described syndrome involving mainly parieto-occipital gray/white matter of the brain. It occurs secondary to various clinical entities, like hypertension and immunosuppressive therapy. Few cases after combination chemotherapy have been reported. This study describes a 36-year-old woman with primary refractory T-cell lymphoma, who developed central nervous system toxicity due to treatment with intrathecal methotrexate and intravenous ifosfamide, idarubicine and etoposide given as a salvage regimen. Both clinical features as well as magnetic resonance imaging findings were typical for posterior leukoencephalopathy syndrome. The patient died despite anti-hypertensive therapy and haemodialysis. Central nervous system toxicity related to chemotherapeutics and posterior leukoencephalopathy syndrome are discussed briefly.

Good tolerance of weekly irinotecan in a patient with metastatic colorectal cancer on chronic hemodialysis.

Pharmacokinetic properties of many antineoplastic agents or their metabolites change with organ dysfunction. Unfortunately, chemotherapy doses determined in phase I and II studies in patients with normal hepatic and renal reserves are not usually applicable to those with hepatic and/or renal dysfunction. Considering the high incidence of colorectal adenocarcinoma, it is not unusual for a colorectal cancer patient to be on chronic hemodialysis. We report a patient with metastatic colorectal cancer on chronic hemodialysis who tolerated weekly irinotecan at 50 mg/m2 well without significant toxicity. We briefly discuss therapeutic dose modification in such patients.

Myasthenia gravis and lymphoblastic lymphoma involving the thymus: a rare association.

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disease. An association between thymic epithelial neoplasms and MG is well known. However, it is rarely associated with hematologic malignancies. In particular, very few cases of lymphoblastic lymphoma involving the thymus and MG have been reported. Here we report a case T-cell lymphoblastic lymphoma involving the thymus who developed MG after the initial diagnosis. The patient initially presented with a mediastinal mass which was diagnosed as lymphoblastic lymphoma. MG was diagnosed during leukemic relapse in this patient and was based on clinical presentation and neurophysiologic studies including single fiber electromyography (EMG) and repetitive nerve stimulation tests. In contrast to the other cases with such an association, the myasthenic symptoms presented nine months after the diagnosis of lymphoma by thymectomy. The patient had a highly aggressive clinical course and was resistant to various chemotherapy regimens.

Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary.

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.

Accelerated hepatitis C virus replication with rituximab treatment in a non-Hodgkin's lymphoma patient.

The treatment of patients with non-Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B-cell lymphoma who presented with a mass in her left breast. She had had HCV-related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial-spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B-cell lymphomas, we believe that the use of such agents with potentially long-lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.

Coincidental detection of T-cell rich B-cell lymphoma in the paraaortic lymph nodes of a woman undergoing lymph node dissection for cervical cancer.

The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B-cell lymphoma in dissected lymph nodes has not been reported to our knowledge. We report such a case. The biopsy of an exophytic lesion at the uterine cervix showed squamous cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, paraaortic lymph node dissections were performed. Pathologic examination revealed a T-cell rich B-cell lymphoma in some lymph nodes beside squamous cell carcinoma in several of others. ELISA for human immuno-deficiency virus (HIV) was negative. The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy for the lymphoma and concomitant pelvic chemo-radiotherapy with cisplatin for cervical cancer were given. In this rare coincidence; the best available therapy for each of the diseases should be considered individually. We also suggest that HIV screening test be carried out, because both diseases may be related to human immuno-deficiency virus, although our patient was HIV-negative.