Assessing genotoxic effects of chemotherapy agents by a robust in vitro assay based on mass spectrometric quantification of γ-H2AX in HepG2 cells.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents' safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

The Clinical Profile of Newly Diagnosed Acute Myeloid Leukemia at a Tertiary Care Center in South India: A Cross-Sectional Study.

Background and objective Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood malignancy prevalent among both children and adults, accounting for a significant proportion of acute leukemia cases worldwide. Our study aimed to shed light on the demographic and clinical profile and risk stratification of newly diagnosed AML cases at a tertiary care government hospital in South India. Methods We conducted a cross-sectional study involving 221 patients with AML in the Department of Clinical Hematology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai, Tamil Nadu from January 2020 to December 2022. All data were collected from the hospital database of patients' medical records. A thorough analysis of clinical history, comorbidities, laboratories, risk stratification, and chemotherapy regimen was performed. The patients included in the study were newly diagnosed cases of AML over the age of 13 years, and we excluded all the relapsed cases. Results The highest proportion of patients were in the age group of 41-50 years (22.2%), and there was a significant male predominance (55.7%) in the cohort. Occupationwise, 31% of the study population were farmers, followed by housewives (16.3%). While no identifiable risk factors for AML were found in 191 cases (86.4%), 4.1% had undergone previous chemotherapy, and 3.6% had myelodysplastic syndrome (MDS). Hyperuricemia was noted in 50 cases (22.6%) while 8.6% had tumor lysis syndrome (TLS). About 53.8% of cases fell in the intermediate risk category of AML. Standard induction chemotherapy was administered in 87.3% of cases of AML. Conclusions Gaining awareness and knowledge about the regional demographic data and clinical presentation of AML will aid in the early detection, prompt referral, and initiation of treatment, thereby further improving patient outcomes in the era of targeted therapy and hematopoietic stem cell transplantation.

Metastatic Epithelioid Hemangioendothelioma of the Bone: A Case Report and Literature Review.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular tumor, which can pose a diagnostic dilemma. It affects women more than men and is mainly found in the liver, lung, and bone. To date, there are no known predisposing factors. Limited data are available on the management of EHE at metastatic stages. The only optimal treatments to prevent metastatic dissemination are surgical resection and amputation in addition to radiotherapy at early stages. The oncologist in this rare entity plays an important role in the guided and standardized management of this disease, especially for advanced stages. In this article, we report the case of a 74-year-old patient admitted with swelling on the outer aspect of the right calf associated with pain and total functional impairment of the limb. The diagnosis favored a high-risk vascular tumor resembling EHE, confirmed by bone (tibia) and soft tissue biopsy. The patient underwent staging investigations, revealing diffuse metastases to the liver, bones, and lungs. The objective of this article is to advocate for oncological intervention in this entity, particularly in the advanced stages of the disease. Despite its rarity, the advancement of clinical trials and therapeutic recommendations remains crucial for optimal treatment.

Arterial Stiffness Changes in Adult Cancer Patients Receiving Anticancer Chemotherapy: A Real-World Bicentric Experience.

Background Chemotherapy correlates to acute and long-term cardiotoxicity, is reflected clinically by myocardial and vascular endothelial dysfunction, and can cause cardiovascular complications. Thus, early diagnosis of cardiovascular disease in cancer patients undergoing anti-cancer treatment is necessary to enhance long-term survival. Our principal objective in this study was to discern the impact of specific anti-cancer chemotherapeutics and biologics on arterial stiffness alterations before and after the administration. Methods Conducted at Mustafa Bacha University Hospital, Algeria, the study focused on arterial stiffness in anti-cancer chemotherapy patients. Assessments included blood pressure, diabetes, and dyslipidemia, with precise measurements using validated systems, particularly pulse wave velocity (PWV). Various chemotherapy protocols were applied, and statistical analysis with R software (R Foundation for Statistical Computing, Vienna, Austria) maintained a significance level of p=0.05. Key outcomes centered on carotid-femoral PWV and secondary endpoints such as central and peripheral pressures and pulse pressure (PP). Univariate and bivariate analyses were conducted using appropriate statistical tests.  Results A comparative prospective observational study was completed on 58 patients (34 women and 24 men; mean age: 52.64 +/- 12.12 years) treated with anti-cancer chemotherapy agents. Our evaluation included a complete clinical exam, electrocardiogram, Doppler echocardiography, and applanation tonometry with arterial stiffness measurement using PWV. Patients presented significantly higher levels of carotid-femoral PWV, regardless of the chosen chemotherapy protocol, with no return to the initial level after one year of stopping treatment (p-value < 0.01). Moreover, this increase was more significant in patients with diabetes and hypertension and patients treated with monoclonal antibodies or intercalants.  Conclusion This prospective study shows that chemotherapy patients have elevated arterial stiffness, emphasizing the need to assess PWV and monitor cardiovascular risk factors. PP measurement with PWV could improve risk management.

A Review of Hodgkin Lymphoma in the Era of Checkpoint Inhibitors.

Hodgkin lymphoma (HL) is a hematopoietic malignancy of B-cells that has a bimodal distribution with respect to age and incidence. With the introduction of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) and radiation combined, the prognosis of HL has significantly improved, with five-year survival rates approaching 95%. While HL has become highly curable, the side effect profiles of ABVD are dire and warrant continuous review. Because HL is often diagnosed in populations in their 20s-30s, patients are forced to undergo fertility preservation procedures as well as deal with other long-term side effects of chemotherapy (including doxorubicin dose-dependent cardiotoxicity and bleomycin-induced lung toxicity). The opportunity cost of the treatment in the short term and vulnerability to treatment-induced malignancies decades later dramatically affect the quality of life of HL patients. New therapies have developed over the past several decades with respect to immunotherapies, particularly programmed death protein 1 inhibitors (e.g., nivolumab and pembrolizumab). Studies have shown checkpoint inhibitors to be effective in treating HL with an objective response rate of 69% for relapsed/refractory classical HL for nivolumab use. Checkpoint inhibitors will continue to help maintain the high five-year survival rate for HL and hopefully have a more favorable side effect profile in the short term, as well as later in the patient's life. This article seeks to summarize treatment options for HL while comparing outcomes and side effect profiles with the addition of checkpoint inhibitors.

Hemophagocytic Lymphohistiocytosis in a Patient With Human Immunodeficiency Virus.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disorder that is often underdiagnosed due to its similarities in other forms of shock, most notably septic shock. In this case report, we discuss a patient who has a history of HIV presenting with altered mental status and cytopenias, ultimately going into shock and passing away. We initially thought we would be dealing with a case of septic shock, but a diagnostic workup during his hospital case lead to a diagnosis of hemophagocytic lymphohistiocytosis. This case illustrates how patients with HLH present very similar to septic shock and how to manage patients with this very aggressive disease.

Outcomes of a Undiluted, One-Bag Desensitization Protocol for Chemotherapeutic Agents.

BACKGROUND: Hypersensitive reactions (HSRs) often require that the provoking medication be discontinued but chemotherapeutic drugs are often essential for the treatment of the disease. Rapid drug desensitization is a procedure that induces temporary tolerance to the drug allowing continuation of treatment in patients who have presented HSRs. Most of the desensitization protocols use 3 bags with sequential dilutions of the drug, which are infused in gradual steps. However, it has not been sufficiently investigated whether dilution is essential for successful desensitization. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of a new one-bag desensitization protocol which uses a single solution of 1 mg/mL throughout the procedure allowing to reduce time and simplifying the desensitization procedure. METHODS: Retrospective observational study was carried out in adult patients with HSRs to chemotherapy agents who received a new nondilution one-bag desensitization protocol between 2016 and 2021. RESULTS: A total of 130 desensitization procedures with an undiluted one-bag protocol were performed on 17 patients with HSRs to chemotherapy. One hundred and seven (82.3%) were for desensitization to CBDCA, 15 (11.5%) for oxaliplatin, 4 (3.1%) for paclitaxel and 4 (3.1%) for brentuximab. All of the 130 procedures were successfully accomplished, and all patients could receive their target dose. No breakthrough reactions (BTRs) occurred in 77% (100/130) of desensitizations, and only mild reactions (grade 1) with skin symptoms were observed in 23% (30/130) of desensitizations. CONCLUSION AND RELEVANCE: The undiluted one-bag desensitization protocol was safe and effective and has been adopted as the standard of care at our institution in treating patients with HSRs to chemotherapeutic drugs as it requires less time and simplifies the desensitization procedure, optimizing risk management.

Atypical Carcinoid Syndrome in a Patient Presenting With Pericarditis and Supraventricular Tachycardia: A Case Report.

Atypical carcinoids are more uncommon than typical carcinoids, and carcinoid syndrome in general is quite rare. Mediastinal atypical carcinoid is a rare neuroendocrine tumor (NET) that spreads aggressively and rapidly. Morphologically, neuroendocrine tumors are classified into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma, and the latter two are high-grade tumors. The incidence of atypical carcinoid is rare, and the prognosis is poor, which makes larger trials difficult. It may affect the liver, lungs, or mediastinum with or without metastasis. We present a case of a 47-year-old male patient who presented with chest pain and was found to be in supraventricular tachycardia (SVT) on initial presentation to the hospital. A repeat electrocardiogram (ECG) showed widespread ST-segment elevation. A bedside echocardiogram showed a moderate pericardial effusion, and the patient underwent a coronary angiogram, which showed normal coronary arteries. A computed tomography pulmonary angiogram (CTPA) showed a right mediastinal mass, and the patient was referred to oncology following a discussion in a multidisciplinary team (MDT) meeting. He was commenced on neoadjuvant chemotherapy and has been followed up since in the outpatient clinic. This case is unique due to the initial presentation of supraventricular tachycardia and pericardial effusion.

A Rare Case of Stage IV Mixed Neuroendocrine Small Cell and Adenosquamous Cell Carcinoma of the Gallbladder.

Gallbladder (GB) carcinoma is the fifth most common type of gastrointestinal cancer. Although a majority of these cancers are found to be adenocarcinomas, we present a rare case in which the GB carcinoma was found to have mixed histology with both small cell neuroendocrine carcinoma and adenosquamous cell carcinoma.

Evaluation of Closed System Transfer Devices in Preventing Chemotherapy Agents Contamination During Compounding Process-A Single and Comparative Study in China.

Aim: We performed a comparative study to investigate the efficacy of closed system transfer devices (CSTDs) on the safe handling of injectable hazardous drugs (HDs). Methods: The exposure assessments of cyclophosphamide and cytarabine were performed under traditional or CSTDs. For preparation activity, chemotherapy contamination samples on protective equipment (such as gloves and masks) were collected. The contamination analysis was performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). A 6-item form was distributed monthly (form M1-M6, total 6 months) to assess the pharmacists' experience on ergonomics, encumbrance, and safety impression. Results: Totally, 96 wiping samples were collected throughout the study. The numbers of contaminated cyclophosphamide samples reduced under CSTD were -37.8, -41.6, -67.7, -47.3, and -22.9% and cytarabine were -12.3, -12.1, -20.6, -69.6, and -56.7% for left countertop, right countertop, medial glass, air-intake vent and door handle, as compared to traditional devices. The reduction was similar to pharmacist devices, i.e., -48.2 and -50.0% for masks and gloves cyclophosphamide contamination, -18.0 and -42.4% for cytarabine. This novel system could improve contamination on dispensing table, transfer container, and dispensing basket by -16.6, -6.0, and -22.3% for cyclophosphamide and -28.5, -22.5, and -46.2% for cytarabine. A high level of satisfaction was consistently associated with ergonomics for CSTD during the compounding process. Meanwhile, a slightly decreased satisfaction on ergonomics, encumbrance, and safety impression was observed for the traditional system between M2 and M3. Conclusion: Closed system transfer devices are offering progressively more effective alternatives to traditional ones and consequently decrease chemotherapy exposure risk on isolator surfaces.

Immature Teratoma With Metastatic Gliosis.

Immature teratomas are rare malignant tumors of the ovary. They are made of immature components of germ cell origin. The incidence of immature teratomas is highest in young adults aged 18 to 39. The prognosis heavily depends on the International Federation of Gynecology and Obstetrics (FIGO) staging system and is influenced by factors such as cell type, tumor grade, capsular rupture, and metastatic risk factors. Initial treatment is complete surgical resection. When indicated, platinum-based adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP) is the treatment of choice. Next-generation sequencing of the tumor can influence treatment in the recurrent setting. Temozolomide is an alkylating agent used to target high-grade gliomas. Bevacizumab is a targeted therapy that interferes with the process of angiogenesis by inhibiting vascular endothelial growth factor (VEGF). We report a 36-year-old female who presented with a 17.6cm x 10.5cm x 24.2cm intraabdominal mass and ascites. Upon tumor resection, she was found to have a stage IIIa, grade 2 immature teratoma of the left ovary, with glial tissue being the metastatic cell type. Disease progression continued despite treatment with BEP. She was then treated experimentally with six months of bevacizumab and temozolomide, given its rarity and targeted therapy for glial tissue. Despite monoclonal antibody therapy, the tumor progressed again and was treated with docetaxel and gemcitabine. A repeat CT of the chest, abdomen, and pelvis demonstrated scattered peritoneal implants that were increasing in size. Chromosome analysis was performed and revealed somatic mutations of MLH1, MSH2, MSH6, and PD-L1. The patient has requested a break from chemotherapy but will be treated with direct immunotherapy when she restarts. This case's importance lies in its rarity because fewer than 10 cases of immature teratomas with metastatic glial tissue are noted in the world's literature. Furthermore, this is the first reported case of this cell type being treated with immunotherapy in the world literature.

Small Bowel Obstruction Due to Metastatic Urachal Adenocarcinoma: A Rare Presentation.

Urachal adenocarcinoma is a rare but highly malignant epithelial cancer that accounts for <1% of all bladder malignancies and commonly presents with hematuria. We report a case of metastatic urachal adenocarcinoma presenting as bowel obstruction. A 54-year-old male patient with a history of alcohol abuse presented to the emergency with acute-onset, diffuse, cramping abdominal pain, worst in the epigastrium and lasting one day. Abdominal examination revealed moderate guarding and generalized tenderness with hypoactive bowel sounds. Imaging confirmed an evolving small bowel obstruction and a urachal remnant with a superimposed mass lesion. The patient underwent an exploratory laparotomy and a high-grade small bowel obstruction due to the mass was identified. An intraoperative frozen section identified adenocarcinoma. A biopsy of the urachal mass confirmed urachal adenocarcinoma. The final diagnosis was moderately differentiated urachal adenocarcinoma. The tumor was deemed unresectable due to the involvement of multiple loops of the small bowel and the mesentery of the small and large bowels. Systemic chemotherapy with 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (modified FOLFOX-6) was initiated. Our patient did not report any prior urinary symptoms or recurrent abdominal pain, which are the common symptoms that urachal adenocarcinoma presents with. Bowel obstruction is a rare presentation of urachal adenocarcinoma since the spread of the disease to the viscera occurs much later in the course. This case report highlights a rare presentation of an even rarer malignancy.

Changes in systemic cancer therapy in Australia during the COVID-19 pandemic: a population-based study.

BACKGROUND: Since the emergence of COVID-19 there have been increasing global concerns about delays and/or discontinuations in cancer care. However, it is unclear to what extent systemic cancer therapy was impacted by COVID-19 in countries with relatively low COVID-19 infection rates. We examined changes in systemic cancer therapy in Australia during the COVID-19 pandemic. METHODS: We conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between January 2017 to December 2020. We reported monthly dispensing and initiation rates of antineoplastic (chemo-, immuno- and targeted therapy), endocrine and supportive medicines per 100,000 population. We reported monthly discontinuation rates (defined as ≥90 days gap between cancer medicine dispensings) per 1,000 people treated. We used interrupted time series analysis to examine changes during times of increased COVID-19 risk and related public health measures (March, April and July 2020). FINDINGS: Between January 2017 and December 2020, 1,011,255 cancer medicines were dispensed to 51,515 people. Overall, there were no reductions in antineoplastic dispensing or initiation during the COVID-19 pandemic. In March 2020, we observed a temporary increase of 39/100,000 (95% CI: 14 to 65/100,000) in antineoplastic dispensing, driven by immunotherapy and targeted therapy. In April 2020, we observed a temporary decrease in chemotherapy initiation (-2/100,000, 95% CI: -4 to -1/100,000) and temporary increase in discontinuation of all antineoplastic medicines (35/1,000, 95% CI: 20 to 51/1,000), but these changes were not sustained. INTERPRETATION: The effective control of COVID-19 in Australia appears to have mitigated the initial impact of COVID-19 on systemic cancer therapy. We observed only small and temporary changes in the use of some cancer medicines early in the pandemic. FUNDING: National Health and Medical Research Council; National Breast Cancer Foundation; Translational Cancer Research Network, supported by the Cancer Institute NSW.

Outcomes of systemic therapy in metastatic phyllodes tumor of the breast.

PURPOSE: Metastatic phyllodes tumors of the breast (MPT) are rare breast neoplasms, limiting development of standardized treatment approaches. We sought to characterize the largest group of MPT thus far reported, evaluating systemic therapy outcomes. METHODS: Adult patients diagnosed with MPT between 1993 and 2015 and followed at MD Anderson Cancer Center were selected for retrospective chart review. Systemic therapy was sorted into: adriamycin/ifosfamide (AI), other anthracycline regimens, other ifosfamide regimens, gemcitabine-based regimens, and other. Given one patient may have received more than one regimen, we assumed that the effects of each regimen were independent from previous therapy. Median overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Log-rank test was performed to evaluate the difference in OS between patient characteristics groups, and the differences in PFS between the five chemotherapy regimens. RESULTS: We identified 50 MPT patients, with 31 patients receiving 61 systemic regimens. Median OS was 10.7 months (95% CI: 8.67, 16.5). AI had a PFS of 9.10 months (95% CI: 5.03, 14.2), other ifosfamide regimens had a PFS of 5.10 months (95% CI: 0.67, 12.1), other anthracycline regimens had a PFS of 3.65 months (95% CI: 1.17, 7.90), gemcitabine-based regimens had a PFS of 2.80 months (95% CI: 1.83, 4.60), and other regimens had a PFS of 1.67 months (95% CI: 1.13, 7.77). CONCLUSION: MPT patients are a unique population with limited characterization to date. Our study demonstrates activity of multiple sarcoma-directed chemotherapy regimens, with ifosfamide-containing regimens having the longest PFS.

Advanced Medical Devices for Preparation and Administration of Chemotherapeutic Agents: Results from a Multi-Dimensional Evaluation.

PURPOSE: To evaluate the incremental benefits concerning the implementation of closed-system medical devices for the preparation and administration of chemotherapy agents (integrated or not with traceable workflow), within an Italian clinical practice, in which the use of such technologies is not standardized. METHODOLOGY: Four Scenarios, implying different levels of technologies introduction, were analyzed, based on the presence and/or absence of closed systems and traceable workflow, in the preparation and in the administration phase. A literature review was conducted, in order to retrieve efficacy and safety measures. Economic and organizational benefits, assuming a hospitals perspective, were assessed by means of health-economics tools, considering 27,660 (±695.86) drugs on average prepared, on an annual basis, by 12 hospitals involved. The typology of medical devices and other devices/equipment used, the human resources involved, and the time spent for the preparation and administration phases were collected. RESULTS: Literature stated that the introduction of advanced technologies (CSTDs in the preparation phase, closed-system in the administration phase, both integrated by a traceable workflow) could: i) decrease surface contamination (12.24% vs 26.39%, P<0.001) and ii) improve the capability to identify dosage errors (7% vs 0.096%, P<0.05). The above technologies presented the best trade-off between cost sustained and efficacy gained. Despite marginal investments (ranging from +1% to +6%) being required for their acquisition, an organizational saving equal to more than 1,000 working hours emerged, which could be spent on other hospital activities. CONCLUSION: The implementation of closed systems, integrated with a traceable workflow grounding on gravimetric control, may be considered a valid technological alternative within the investigated setting. The marginal incremental costs could be absorbed already in the first year after their introduction, in particular, because of the potential time saving in using closed systems in both the preparation and administration phases, demonstrating the sustainability and feasibility of such advanced technologies.

Redefining Role of 5-Fluorouracil and Exploring the Impact of Taxanes and Cisplatin in Locally Advanced and Recurrent Carcinoma Cervix in Concurrent Setting With Radiotherapy: A Literature Review.

Cervical carcinoma is the fourth most frequent cancer among women worldwide while it is common in rural India. The irony of the situation is that it continues to present in a locally advanced stage with bulky disease posing a significant challenge to the current treatment modalities despite various screening programs. Concurrent chemoradiotherapy is the mainstay of treatment for locally advanced carcinoma cervix. However, the appropriate dosing schedules, along with the salutation of the chemotherapeutic agent, remain a matter of debate to date. The use of chemotherapy in the neoadjuvant and adjuvant setting promises to improve progression-free survival and overall survival. The article aims to review various chemotherapy and their regimens in the treatment of carcinoma of the cervix.

Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy.

BACKGROUND/AIM: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. METHODS: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. RESULTS: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. CONCLUSION: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.

The state of hepatic artery infusion chemotherapy in the management of metastatic colorectal cancer to the liver.

Hepatic artery infusion (HAI) chemotherapy is a locoregional therapy for colorectal cancer liver metastasis that has been available since the 1980s. Multiple clinical trials have demonstrated the safety and efficacy of HAI with higher response rates compared to systemic chemotherapy alone. Clinical trials have shown the benefit of using HAI as a bridge to conversion to resection at a higher rate than systemic chemotherapy alone with rates as high as 60% in heavily pretreated patients. HAI in combination with systemic chemotherapy has also been associated with prolonged recurrence free survival and overall survival in the adjuvant setting. Specifically, the addition of HAI continues to show a benefit in prolonging overall survival, despite increased effectiveness of modern systemic chemotherapy (i.e., oxaliplatin and irinotecan). Lower recurrence and improved survival rates associated with HAI and systemic chemotherapy persist regardless of RAS mutational status.

Transformation kinetics of cyclophosphamide and ifosfamide by ozone and hydroxyl radicals using continuous oxidant addition reactors.

The detection of pharmaceuticals in water and wastewater has triggered human and ecological health concerns. As highly toxic compounds, chemotherapy agents (CAs), such as the cyclophosphamide (CYP) and ifosfamide (IFO) structural isomers, represent a unique threat. This research elucidated the fate of CYP and IFO during ozonation and advanced oxidation by hydroxyl radicals (HO•). Novel semi-batch reactors were used to determine the second-order rate constants for CYP and IFO with O3 and HO•. These reactors provided independent control of the oxidant exposure through continuous and constant aqueous ozone and peroxone (O3-H2O2) addition. The rate constants for transformation of CYP and IFO by ozone were 2.58 ± 0.40 M-1s-1 and 6.95 ± 0.21 M-1s-1, respectively, indicating that ozone alone is not suitable for treating CAs. Transformation of CYP and IFO by hydroxyl radicals was fast, with rate constants of 2.69(±0.17)×109 M-1s-1 and 2.73(±0.16)×109 M-1s-1, respectively. The major transformation products formed by O3 and HO attack consisted of the 4-hydroxy-, 4-keto-, dechloroethyl-, and imino- derivatives of CYP and IFO. Low yields of the active metabolites of the CAs, namely phosphoramide mustard and isophosphoramide mustard, were detected. These findings suggest that treated water may retain the ability to alkylate DNA and confer toxicity.

Behaviour and Prevention of 5'Fluorouracil and Doxorubicin-induced Oral Mucositis in Immunocompetent Patients with Solid Tumors: A Randomised Trial.

PURPOSE: This study evaluated the efficacy of four methods to prevent chemotherapy-induced oral mucositis (OM) in patients with solid tumors (ST). In addition, the behaviour of OM was investigated in these oncological patients. MATERIALS AND METHODS: Forty-eight patients, aged 27-84, were randomly allocated to different groups from the first day of chemotherapy (CT), in the following sequence: group 1: intensive oral care programme (IOCP); group 2: 0.12% chlorhexidine mouthrinse; group 3: 0.03% triclosan mouthrinse; group 4: low-level laser therapy (LLLT). Oral mucositis was evaluated on the 7th and 14th days by means of the Oral Mucositis Assessment Scale (OMAS). RESULTS: Thirty-one (64.5%) patients developed OM in the first cycle of CT and the pain was significantly associated with OM severity (p < 0.0001). The statistically significantly worst OMAS score was found for the lips and buccal mucosa (p < 0.0001). Despite a lack of statistical significance, IOCP and LLLT notably demonstrated potential effects to prevent OM in patients who presented with only oral erythema (75%) and lower peak of severity during the follow up, respectively. CONCLUSIONS: Improved oral care awareness is needed in patients undergoing 5'fluorouracil and doxorubicin, mainly to avoid pain caused by oral mucositis. Oral mucositis was more prevalent and aggressive in oral sites exposed to chronic trauma. The IOCP and LLLT approaches showed positive results to prevent oral mucositis and should be further investigated in similar and larger samples.