Modern Chemotherapy

Journal Information
ISSN / EISSN : 2169348X / 21693498
Current Publisher: Scientific Research Publishing, Inc. (10.4236)
Total articles ≅ 15
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Latest articles in this journal

Nawfel Mellas, Fatimzahra Hijri, Zineb Benbrahim, Omar El Mesbahi, Nabil Ismaili
Modern Chemotherapy, Volume 3, pp 5-9; doi:10.4236/mc.2014.31002

Chemotherapy and targeted therapy remain the cornerstone of treatment of locally advanced and metastatic non-small cells lung cancer (NSCLC). Given the intrinsic chemoresistance of tumor cells, new treatment options have been developped. The knowledge of the molecular mechanisms of tumor biology, and signal transduction pathways activating cancer cells led to the identification of a new targeted therapy such as Crizotinib. The small molecule Crizotinib is a selective inhibitor of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase) and its oncogenic variants (ALK fusion gene and some mutations of ALK). Phases I and II trials showed the efficacy of Crizotinib in the treatment of locally advanced and metastatic NSCLC expressing ALK. Thereafter, randomized Phase III trial confirmed the significant superiority of Crizotinib versus standard chemotherapy in terms of progression free survival and objective response with good tolerance; therefore, it has been approved by the Food and Drug Administration (FDA) as the standard treatment for locally advanced and metastatic ALK-positive NSCLC.
Ka-On Lam, Betty Tsz-Ting Law, Ra Lai-Wan Kwong
Modern Chemotherapy, Volume 3, pp 11-19; doi:10.4236/mc.2014.32003

Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.
F. Dagbert, Y. J. McConnell, E. Carmona, L. Sideris, J. P. Hallé, P. Dubé
Modern Chemotherapy, Volume 3, pp 1-4; doi:10.4236/mc.2014.31001

Introduction: Improved drug delivery mechanisms for the treatment of residual peritoneal cancer cells following cytoreduction surgery are needed. Alginate microcapsules are a potentially useful mechanism for delivery of bioengineered cells, but when injected into the peritoneum, their distribution and properties are not well described. Methods: Aliquots of 300, 600 or 1200 microcapsules were injected into the peritoneum of 81 mice. Mice were sacrificed at 6, 12, 18, and 48 days and laparotomy was performed to quantify the distribution of microspheres. Results: The injections were well tolerated for up to 48 days. No peritoneal adherence or inflammatory reaction was noted to the microcapsules. Injection of 1200 microcapsules resulted in a better overall persistence and widespread peritoneal distribution at up to 48 days. The volume of fluid used for injection of the microcapsules did not affect their distribution or persistence. Conclusion: The intraperitoneal injection of alginate microspheres allows wide and persistent distribution throughout the abdominal cavity. The next step is to test the distribution of microcapsules when delivered following surgery in a rodent model.
Bill Cham
Modern Chemotherapy, Volume 2, pp 33-49; doi:10.4236/mc.2013.22005

In the last century, the discovery of cytotoxic agents was revolutionary for anticancer therapy. These therapies have resulted in better understanding of cancer in general. However, the development of agents that combine efficacy, safety and convenience remains a great challenge. The narrow, if not adverse, therapeutic index of most drugs, the damage not only to cancer cells, but also to normal and healthy tissue and the occurrence of resistance have limited anticancer efficacy. This review presents the development of promising novel cytotoxic solasodine rhamnosyl glycoside drugs that offer not only gains in specificity and efficacy, but also in safety, tolerability, non-resistance and convenience in the treatment of patients with cancer.
Noriko Yoshimura, Koji Arihiro, Shunsuke Takahagi, Michihiro Hide
Modern Chemotherapy, Volume 2, pp 66-68; doi:10.4236/mc.2013.24008

Advanced Extramammary Paget’s disease (AEMPD) shows a poor prognosis despite multimodality therapy. In recent years, it is suggested that anti-HER2 therapy may be promising for HER2-positive AEMPD. We herein present an autopsy case of a patient with AEMPD treated with multimodality treatment including anti-HER2 therapy. A 78-year-old man who diagnosed with AEMPD died after surgery and systemic chemotherapy including anti-HER2 therapy (trastuzumab). The metastatic skin lesions were immnohistologically HER2-positive. While the patients were administrated trastuzumab plus taxan (docetaxel, and paclitaxel) regimen, the metastatic skin lesion decreased, however, brain metastases were found in his brain and trastuzumab is discontinued. The skin metastasis rapidly spread over his body, leading to weakness, and he eventually died. At autopsy, the lesions of EMPD were extended distant organs including brain, although each metastasis was small and asymptomatic. The wide lesion of skin metastasis was exacerbated after discontinuation of trastuzumab, and transudate was observed due to the extensive necrosis and erosion. Our autopsy findings showed one progressive pattern of AEMPD, and indicated what is the clinical and pathological significance of anti HER2 therapy for HER2-positive AEMPD.
Eguzo Kelech, Chisara C. Umezurike, Emmanuel Akwuruoha
Modern Chemotherapy, Volume 2, pp 69-72; doi:10.4236/mc.2013.24009

Background: Choriocarcinoma is a rare clinical condition, and its diagnosis may be difficult, especially in resource-limited settings. Case Presentation: A 38-year old para 2 woman is with a 4-month history of intractable vaginal bleeding and offensive vaginal discharge, but without antecedent pregnancy. She had previously been managed at various tertiary medical institutions where several pelvic ultrasound scans and even histology of endometrial curette could not clinch the diagnosis. The diagnosis of choriocarcinoma was made by a serial strip-based pregnancy testing, which was still positive at 1:200 dilutions. She was treated with chemotherapy involving Adriamycin, Cyclophosphamide, Methotrexate and Folinic acid. Conclusion: The diagnosis of choriocarcinoma may be difficult especially when it develops ab initio without preceding abortion, molar or term pregnancy. In settings where serum hCG assay may be not available, the simple strip-based pregnancy test in dilution could be helpful in its diagnosis and treatment monitoring.
Hideki Takeshita, Koji Chiba, Sachi Kitayama, Shingo Moriyama, Rika Omura, Akira Noro
Modern Chemotherapy, Volume 2, pp 1-7; doi:10.4236/mc.2013.21001

Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment for patients who fail these firstline chemotherapies is unavailable. We examined the efficacy and safety of secondline paclitaxel, gemcitabine, and cisplatin (PCG) chemotherapy in Japanese patients. Methods: Between 2004 and 2010, 25 patients with metastatic UCs who failed to respond to platinumbased regimens were treated with PCG. They received intravenous paclitaxel (60 mg/m2) and gemcitabine (1000 mg/m2) on days 1 and 8, and cisplatin (70 mg/m2) on day 2 of every 21 day course. We retrospectively collected patients’ clinical and pathological data and evaluated adverse effects and survivals. Results: Patients underwent 95 PCG cycles in all (average, 3.8 cycles per patient). One patient (4%) achieved complete response, 5 (20%) showed partial response, 8 (42%) had disease stabilization, and 5 (26%) had disease progression. Median overall survival was 8.5 months. Neutropenia and thrombocytopenia of grade ≥ 3 were observed in 68% and 56% of patients, respectively. No treatment related death occurred. Multivariate analysis revealed that hemoglobin levels 1.73 m2) were significant risk factors for overall survival. Conclusion: PCG chemotherapy in the secondline setting potentially contributed to good prognosis in selected patients with relatively significant but tolerable toxicity.
Carmen Viada Gonzalez, Jean-François Dupuy, Martha Fors López, Patricia Lorenzo Luaces, Gisela González Marinello, Elia Neninger Vinagera, Beatriz García Verdecia, Tania Crombet
Modern Chemotherapy, Volume 2, pp 51-56; doi:10.4236/mc.2013.23006

Time-to-event has become one of the primary endpoints of many clinical trials. Comparing treatments and therapies using time-to-event (or “survival”) data requires some care, since survival differences may occur either early or late in the follow-up period, depending on various factors such as the initial potency or the duration of efficacy of the drugs. In this work, we investigate the effect of the CIMAvax?EGF vaccine therapy on the survival of patients with non-small cell lung cancer, using stratified and unstratified weighted log-rank tests. Weighted log-rank tests are designed to identify early and late survival differences between treatments. Using these tests, we conclude that the vaccine is more efficient than the standard therapy among patients less than 60 years of age.
Anders K. Boysen, Bettina R. Jensen, Laurids O. Poulsen, Soren Ladefoged
Modern Chemotherapy, Volume 2, pp 8-14; doi:10.4236/mc.2013.21002

Aim: Management of febrile neutropenia is challenged by lacking microbiological and clinical documentation of infection. Procalcitonin is emerging as a new promising biomarker of infection. We aimed to undertake a systematic review evaluating the diagnostic accuracy of procalcitonin as a marker of infection in febrile neutropenia. Methods: We performed a systematic re- view of the literature using the databases MEDLINE, EMBASE and Cochrane Library including a search of the grey literature (e.g. unpublished data, web sides of relevant societies). The methodological quality was assessed using predefined criteria. The relevant data were extracted and analyzed by two authors. Results: The literature search yielded a total of 193 studies of which nine were eligible for inclusion. There was a great variation in the quality of the methodological design. A notable heterogeneity exists regarding the studied populations and the definition of the reference standards. Among the nine included studies the sensitivity ranged from 42% to 72% and the specificity ranged from 64% - 89% at a cut off value ranging from 0.5 - 0.8 ng/ml. The studied endpoint was either microbiologically or clinically documented infection. Four studies found procalcitonin superior to Creactive protein in discriminating infection from the various other causes of fever. Conclusion: Procalcitonin appears to be a promising biomarker and might add new diagnostic information in the management of febrile neutropenia.
Eugenia Girda, Rebecca Phaeton, Gary L. Goldberg, Dennis Y. S. Kuo
Modern Chemotherapy, Volume 2, pp 15-18; doi:10.4236/mc.2013.22003

Objective: The objective of this study is to assess the outcome of port-a-cath (PAC) maintenance every three months in patients with gynecologic malignancies with the goal of standardizing a safe and appropriate interval that would maintain patency and minimize side effects. Methods: We performed a retrospective medical record review and evaluation of all patients with a Bard? PAC who were noted to have no evidence of disease (NED) during the years 2003 to 2010. The interval between accessions and any complications related to the presence of the PAC were recorded. Relevant complications included skin infections, bacteremia, thrombosis, and occlusions. Statistical analysis was done using the Fisher’s exact test. Results: A total of 201 patients had PAC placed and 43 patients underwent PAC accessions to maintain patency. The total number of accessions was 150 with a median number per patient of 2.0 (range 1 - 10). The mean time between flushes was 112 days (SD = 57). When comparing women in maintenance who had flushes within 90 days versus those who had flushes over 90 days apart, there was no difference in infection or occlusion rates between these groups (p = 0.515). In the Conclusion: Infections and occlusions are rare in women with gynecologic malignancies undergoing maintenance of their PAC. Longer intervals between PAC flushes do not appear to affect the outcome in our patients. Our ongoing data and follow-up confirm that extending the interval of PAC accession to every 3 months, rather than monthly, is safe, effective and convenient in the patient population with gynecologic malignancies.
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