Chemotherapy (Chemotherapy )

Publisher: International Society of Chemotherapy, Karger


This journal publishes the results of investigations into the mode of action and pharmacologic properties of antibacterial, antiviral and antitumor substances. Although experimental work predominates, clinical studies are included. Papers selected for the journal offer data concerning the efficacy, toxicology, and interaction of new drugs in single and combined applications. The journal also publishes studies designed to determine pharmacokinetic properties or evaluate the comparative efficacy of similar preparations. The growth of chemotherapeutic applications is well served through the large number of contributions published in each issue and regular supplement issues devoted to specific themes concerning antibiotic and cytostatic chemotherapy.

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The anti-inflammatory drug diacetyl rhein has been found to possess promising antistaphylococcal effects against various drug-resistant strains in our previous study. In the present work, we explored the in vitro combinatory interactions of diacetyl rhein with oxacillin and tetracycline against 13 standard strains and clinical isolates of Staphylococcus aureus, including those resistant to erythromycin, methicillin and tetracycline. Methods: Minimum inhibitory concentrations were determined by broth microdilution assay, and the effects of combinations were evaluated according to the sum of fractional inhibitory concentrations (ΣFICs). Results: Synergistic or additive effects were observed against all S. aureus strains (ΣFIC 0.258-1), whereas diacetyl rhein-oxacillin appeared to be the most effective combination, synergistically inhibiting the growth of 4 strains tested. Conclusion: To our best knowledge, this is the first report on a synergistic antibacterial effect of diacetyl rhein. Our results suggest this promising compound for further evaluation of its synergistic anti-infective potential as an agent with a combined anti-inflammatory and synergistic antibacterial action.
    Chemotherapy 09/2014; 59(6):447-452.
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    ABSTRACT: Background: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. Methods: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. Results: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. Conclusions: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression. © 2014 S. Karger AG, Basel.
    Chemotherapy 07/2014; 59(6):407-413.
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    ABSTRACT: Background: We investigated the effects of two antibiotics, erythromycin and rifampicin, on the immunomodulatory gene expression and cellular function of human polymorphonuclear leukocytes (PMNs). Methods: We used real-time quantitative PCR to examine the expression of immunomodulatory genes. The production of reactive oxygen species (ROS) was determined by fluorescence-activated cell sorting. PMN chemotaxis was analyzed using a KK chemotaxis chamber. Results: Stimulation of PMNs with lipopolysaccharide (LPS) resulted in increases in the mRNA levels of immunomodulatory genes. Rifampicin significantly inhibited the overexpression of TLR2, TLR4, CD14 and IL8Rs. However, erythromycin suppressed only the upregulation of TLR2 and TNFA. Neither antibiotic had an effect on the production of ROS. Rifampicin significantly inhibited PMN chemotaxis, but erythromycin had no effect. Conclusions: Erythromycin and rifampicin may play anti-inflammatory roles by affecting the expression levels of immunomodulatory genes or the chemotaxis of PMNs. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(6):395-401.
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    ABSTRACT: Background: The neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, laninamivir and peramivir are available in Japan. However, the selective use of NAIs for treating outpatients with influenza has not been clearly defined. Methods: We assigned 191 patients with influenza to 4 groups, each treated with a different NAI, and then compared how long it took to alleviate fever and other symptoms and to eliminate the virus. Results: Alleviation of fever occurred significantly sooner with peramivir than with either zanamivir (p = 0.0002) or oseltamivir (p = 0.0059), but was not significantly different from that with laninamivir (p = 0.0457; p < 0.0083). Other symptoms were also alleviated sooner by peramivir than by the other 3 NAIs. Conclusions: The ability of each NAI to alleviate influenza symptoms and fever varied. The appropriate use of NAIs requires further study. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(5):373-378.
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    ABSTRACT: Purpose: Capecitabine has demonstrated significant activity in metastatic breast and colorectal cancer. During the course of treatment with capecitabine, we observed that a relevant number of patients developed elevated levels of the mean corpuscular volume (MCV) of red blood cells. Methods: This retrospective analysis reviewed treatment with capecitabine in 35 patients with histologically proven advanced breast and colon cancer. After 9 weeks of treatment, restaging was performed using the criteria proposed by the Committee of the Response Evaluation Criteria in Solid Tumours. Results: Prior to the first cycle of capecitabine treatment, there were no abnormalities in red blood cells, white blood cells, haemoglobin or platelets. The median haemoglobin level prior to the first cycle was 13 g/dl and the MCV (normal range 80-98 fl) was 86.5 fl in colon cancer patients and 12.8 g/dl and 88.7 fl in breast cancer patients, respectively. During the course of treatment, 12 weeks after the baseline evaluation, an increase in MCV was documented, while haemoglobin levels remained stable. An MCV increase was documented between baseline and the end of treatment. We noticed an increase in MCV at the end of treatment both in patients with stable disease or a partial response (n = 17) compared to patients with tumour progression (n = 11) at the first evaluation (12-14 weeks). Discussion: Preliminary results showed that there is a significant MCV increase in patients receiving capecitabine for metastatic colon and breast cancer after 12 weeks of treatment. However, when we compared the MCV rise after 12 weeks that occurred with stable disease or a partial response compared to that in patients with disease progression at the first evaluation, the analysis was not statistically significant. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(5):369-372.
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    ABSTRACT: Background: The aim of this study was to evaluate the efficacy and tolerability of hepatic arterial infusion (HAI) of gemcitabine plus oxaliplatin as second-line treatment for unresectable locally advanced intrahepatic cholangiocarcinoma. Patients and Methods: We retrospectively analyzed the outcome of 12 consecutive patients with unresectable locally advanced intrahepatic cholangiocarcinoma treated with HAI of gemcitabine (1,000 mg/m(2) over 30 min) followed by oxaliplatin (100 mg/m(2) over 2 h), which was repeated every 2 weeks. Results: All patients presented with disease limited to the liver and all had failed at least one line of chemotherapy with gemcitabine and oxaliplatin. The best tumor responses using RECIST criteria were partial responses in 8 patients and stable disease in 3 patients for at least 3 months; in 1 patient, disease progressed, resulting in a disease control rate of 91% (95% CI 45-100%). The median overall survival and time to progression were 9.1 months (95% CI 4.9-8.1) and 20.3 months (95% CI 13.2-49.7), respectively. Partial responses enabled R0 liver surgery in 2 patients and stereotactic radiation therapy in 3 patients. Grade 3/4 toxicities included neutropenia in 2 patients, thrombocytopenia in 2 patients, and oxaliplatin allergy in 2 patients. Conclusions: HAI combining gemcitabine and oxaliplatin showed promising efficacy and safety as second-line treatment for locally advanced intrahepatic cholangiocarcinoma. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(5):354-360.
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    ABSTRACT: Objective: Gemcitabine combined with carboplatin (GC) is a widely used regimen for advanced non-small cell lung cancer (NSCLC), but clinical outcome is still hampered by its toxicity. We conducted a randomized phase II study of GC and compared biweekly versus standard schedules in patients with advanced NSCLC with respect to toxicity and outcome. Methods: Forty patients with stage IIIB or IV NSCLC were randomized to receive either a biweekly regimen of GC [gemcitabine (1,000 mg/m(2) on days 1 and 14) and carboplatin (area under the concentration-time curve, AUC = 3 on days 1 and 14)] every 28 days or a standard regimen of GC [gemcitabine (1,000 mg/m(2) on days 1 and 8) and carboplatin (AUC = 5 on day 1)] every 21 days. These cycles were repeated until disease progression. Results: Response rates were 55% for the biweekly regimen and 40% for the standard regimen. Median overall and progression-free survival times were 19.7 and 6.2 months, respectively, for the biweekly regimen, and 11.8 and 2.8 months, respectively, for the standard GC regimen. Hematologic toxicity was prominent. However, the incidence of grade 1 or 2 thrombocytopenia was significantly lower in the biweekly than in the standard GC regimen (p < 0.05). Nonhematologic toxicity was mild. Conclusion: A biweekly GC regimen was better tolerated than a standard GC regimen in patients with advanced NSCLC. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(5):346-353.
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    ABSTRACT: Background: To reduce the occurrence of medication errors, a systemic approach was developed combining anti-neoplastic medication error reviews and morbidity and mortality conferences (M&MCs). We report the first experience of implementing this strategy in oncology. Methods: The case reports submitted to combined reviews were prepared by physicians and pharmacists, and medication error(s) were described and chronological and root-cause analyses were performed. Results: Ten combined reviews were conducted, which involved the departments of haematology, medical oncology, pneumology, gastroenterology and clinical oncology pharmacy. A total of 91 errors were analysed, of which 3 had reached the patient. Thirty-four corrective actions were proposed; 53% consisted of changes in practice, 35% in procedural reminders and 12% in on-ward education sessions. Conclusions: The combination of medication error reviews and M&MCs appears to be an efficient means of improving cancer patient safety and personnel proficiency. This multidisciplinary work is indispensable to improve future patient management through the critical analysis of past medical errors. © 2014 S. Karger AG, Basel.
    Chemotherapy 04/2014; 59(5):330-337.
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    ABSTRACT: Background: In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice. Methods: Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points. Results: Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone. Conclusions: These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics. © 2014 S. Karger AG, Basel.
    Chemotherapy 02/2014; 59(5):325-329.
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    ABSTRACT: Background: Vancomycin and linezolid therapies are associated with renal dysfunction and thrombocytopenia, respectively. Methods: We retrospectively investigated Japanese patients with renal dysfunction or thrombocytopenia possibly associated with vancomycin and linezolid therapies, including 235 patients treated with parenteral vancomycin and 178 treated with parenteral linezolid. Results: Renal dysfunction occurred more frequently in patients receiving vancomycin (24%) than in those receiving linezolid (13%; p = 0.032), whereas thrombocytopenia occurred more frequently in linezolid-treated patients (41%) than in vancomycin-treated patients (17%; p < 0.001). Controlling trough vancomycin concentrations (<20 μg/ml) protects against renal dysfunction, but thrombocytopenia may occur after >7.5 days of linezolid treatment. Conclusion: Controlling trough vancomycin concentrations to <20 μg/ml protects Japanese patients against renal dysfunction. Linezolid is an appropriate initial therapy for severe infections in patients with acute renal dysfunction, but monitoring of platelet counts is essential after initiation of therapy. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(5):319-324.
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    ABSTRACT: Background: We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma. Patients and Methods: Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m(2), with an increase of 10 mg/m(2) per step, to find the MTD. Results: A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%. Conclusions: The recommended dose of NDP for a phase II study was determined to be 100 mg/m(2). We concluded that our regimen was well tolerated and that the RR was acceptable. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):314-318.
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    ABSTRACT: Background: Although the efficiency of oxaliplatin in patients with advanced ovarian cancer has been demonstrated, it is not commonly used. In cells, oxaliplatin is metabolized by the enzymes belonging to the glutathione-S-transferase (GST) family. Case: A 55-year-old woman with advanced ovarian cancer received 6 cycles of paclitaxel and carboplatin after debulking surgery. Six months later, she experienced a clinical recurrence. A second-line chemotherapy combining 500 mg/m(2) cyclophosphamide with 100 mg/m(2) oxaliplatin was initiated and maintained for 10 cycles. The patient thus experienced a second complete remission that lasted for 6 years. We found that she had deficient GSTM1 enzyme activity with homozygous deletion and normal GSTP1 and GSTT1 activities. Conclusion: The association of a homozygous deletion of GSTM1 with hypersensitivity to oxaliplatin and cyclophosphamide combination chemotherapy has not been described to date in ovarian cancer. Further study of its potential interest to personalized second-line therapy in these patients is called for. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):290-293.
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    ABSTRACT: Background: There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Methods: Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Results: Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Conclusion: Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):307-313.
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    ABSTRACT: Background: Determination of antibiotic resistance of opportunistic Corynebacterium colonizing the nose that cause infections and evaluation of the applicability of a simple method for detecting the most common constitutive-type resistance to macrolides, lincosamides and streptogramin B (MLSB). Methods: 70 isolates colonizing the nose and 70 clinical isolates of various infection sites were used and identified using APICoryne and 16S rRNA. Minimal inhibitory concentrations (MICs) were determined (Etest) for 12 antibiotics. MLSB was defined based on MIC, a simple method using two disks (erythromycin/clindamycin) and detection of the gene erm X (PCR). Results: There was a high percentage - in both groups at the same level - of strains with MLSB (88.5% colonizing the nose and 87.1% causing infections). Detection with the phenotypic method MLSB was confirmed genetically (erm X) in all cases. In both groups, a high percentage of resistance was found to trimethoprim/sulfamethoxazole (in both groups 71.4%), chloramphenicol (nose 44.2%/infections 37.1%), tetracycline (28 and 45.7%) and β-lactam antibiotics (18.5 and up to 32.8%). Conclusion: Differences in antibiotic resistance were found between strains colonizing the respiratory tract and various infections. Isolates from infections more frequently exhibited multidrug resistance. The possibility of using a simple method was confirmed for MLSB detection, which can be applied to determine drug resistance in routine microbiological diagnostics of infections caused by opportunistic Corynebacterium. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):294-306.
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    ABSTRACT: Background/Aims: There is no standard consensus on a strategy in the second-line setting for gemcitabine-refractory advanced pancreatic cancer. This study evaluated the activity and tolerability of oxaliplatin, irinotecan, 5-fluorouracil and leucovorin (FOLFIRINOX) as a second-line therapy in advanced pancreatic adenocarcinoma pretreated with a gemcitabine-based regimen. Methods: A retrospective survey was carried out on 18 patients with advanced pancreatic cancer who had been on gemcitabine-based chemotherapy and were then treated with FOLFIRINOX as a second-line therapy. Results: One patient (5.6%) had a confirmed complete response, 4 (22.2%) had confirmed partial responses and 5 (27.8%) had stable disease, resulting in a rate of disease control of 55.6% (95% CI, 33.3-77.8%). The median progression-free survival and median survival were 2.8 months and 8.4 months, respectively. Seven patients (38.9%) experienced grade 3-4 neutropenia. Grade 3 or 4 nonhematologic adverse events included nausea (38.9%) and vomiting (16.7%). Conclusions: These results suggest the modest clinical activity regarding efficacy and the acceptable toxicity profile with the FOLFIRINOX regimen as a second-line treatment. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):273-279.
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    ABSTRACT: Background: Despite the survival benefit of intraperitoneal (IP) chemotherapy observed in GOG172, significant toxicity and poor treatment completion rates have prevented the widespread acceptance of this regimen. Here, we report our experience with a modified outpatient GOG172 regimen. Methods: Eligible patients had stage III, optimally debulked epithelial ovarian, fallopian tube or primary peritoneal cancer that underwent IP port placement for administration of a modified GOG172 regimen consisting of: (i) intravenous paclitaxel 135 mg/m(2) on day 1 over 3 h; (ii) intraperitoneal cisplatin 75 mg/m(2) on day 2, and (iii) intraperitoneal paclitaxel 60 mg/m(2) on day 8. Day 8 IP paclitaxel was omitted until tolerance of the first cycle of IP cisplatin had been established. Results: Four or more cycles of IP chemotherapy were completed by 72.5% (29) of 40 eligible patients; 20% of patients exhibited catheter-related complications requiring port removal and discontinuation of IP chemotherapy. Grade 3-4 hematologic, metabolic and gastrointestinal toxicities occurred in 36, 8 and 21% of the patients, respectively. With a median follow-up of 47.7 months, progression-free and overall survival was comparable to GOG172. Conclusions: This modified outpatient GOG172 regimen is associated with less toxicity and improved completion rates compared to the original GOG172 regimen. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):251-259.