Infection risk and antimicrobial prophylaxis in bendamustine-treated patients with indolent non-Hodgkin lymphoma: An Australasian Lymphoma Alliance study.

Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.

Prolonged 14-day continuous infusion of high-dose ifosfamide for patients with relapsed and refractory high-grade osteosarcoma: a retrospective multicentre cohort study.

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Clinical Course after Carmustine Wafer Implantation for Newly Diagnosed Adult-type Diffuse Gliomas; A controlled propensity matched analysis of a single center cohort.

PURPOSE: It remains unclear whether combining carmustine wafer (CW) implantation with the standard treatment for adult-type diffuse gliomas is safe and has a prognostic impact. This study aimed to investigate the prognostic value and safety of CW implantation. METHODS: Adult patients with IDH-wild-type and -mutant gliomas, grades 3-4 treated with surgical resection, radiotherapy, and temozolomide chemotherapy between 2013 and 2023 were surveyed. CWs were implanted except in cases of intraoperative wide ventricle opening or marked preoperative brain swelling. For survival analyses, a case-matched dataset based on propensity score matching (PSM), including multiple factors (patient background, diagnosis, and extent of resection) was generated. Progression-free survival (PFS), overall survival (OS), and frequency of complications of CW implantation (brain edema, infection, and cerebrospinal fluid leakage) were compared between the CW and non-use groups. RESULTS: In total, 127 patients (75 in the CW use group and 52 in the non-use group) were enrolled. Regardless of stratification, no significant differences in PFS and OS were observed between the CW use and non-use groups. The frequency of postoperative brain edema was significantly higher in the CW use group than in the non-use group. An adjusted dataset containing 41 patients in the CW use and nonuse groups was generated. Even after PSM, CW implantation had no prognostic effect. CONCLUSIONS: CW implantation with standard treatment demonstrated little beneficial effect for the present strategy of CW use.

Pleuroparenchymal fibroelastosis as a late complication of childhood cancer therapy: A case series.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with distinct clinicopathologic features. It has been associated with exposure to hematopoietic stem cell transplantation (HSCT) and classical alkylating agents. Here, we highlight PPFE as a late complication of childhood cancer therapy by describing the cases of four survivors of childhood cancer with a diagnosis of treatment-related PPFE. All patients received high-dose alkylating agents. PPFE should be considered in the differential diagnosis of restrictive lung disease in patients with history of exposure to alkylating agents or HSCT. Development of PPFE-specific, noninvasive diagnostic tools and disease-modifying therapies will clinically benefit these patients.

A Review of Approaches to Potentiate the Activity of Temozolomide against Glioblastoma to Overcome Resistance.

A glioblastoma (GBM) is one of the most aggressive, infiltrative, and treatment-resistant malignancies of the central nervous system (CNS). The current standard of care for GBMs include maximally safe tumor resection, followed by concurrent adjuvant radiation treatment and chemotherapy with the DNA alkylating agent temozolomide (TMZ), which was approved by the FDA in 2005 based on a marginal increase (~2 months) in overall survival (OS) levels. This treatment approach, while initially successful in containing and treating GBM, almost invariably fails to prevent tumor recurrence. In addition to the limited therapeutic benefit, TMZ also causes debilitating adverse events (AEs) that significantly impact the quality of life of GBM patients. Some of the most common AEs include hematologic (e.g., thrombocytopenia, neutropenia, anemia) and non-hematologic (e.g., nausea, vomiting, constipation, dizziness) toxicities. Recurrent GBMs are often resistant to TMZ and other DNA-damaging agents. Thus, there is an urgent need to devise strategies to potentiate TMZ activity, to overcome drug resistance, and to reduce dose-dependent AEs. Here, we analyze major mechanisms of the TMZ resistance-mediated intracellular signaling activation of DNA repair pathways and the overexpression of drug transporters. We review some of the approaches investigated to counteract these mechanisms of resistance to TMZ, including the use of chemosensitizers and drug delivery strategies to enhance tumoral drug exposure.

Neuropsychological functioning during chemotherapy with temozolomide in high-grade glioma patients: a retrospective single centre study.

PURPOSE: starting from a lack of precise and coherent data in literature, aim of this work is to retrospectively study the influence of chemotherapy with Temozolomide (TMZ) on a wide series of neuropsychological functions in a population of adult high-grade glioma patients. METHODS: an extensive neuropsychological battery was administered pre-operatively (T0) and after 6 (T1) and 12 months (T2) from surgery. After full recovery from surgery, TMZ was delivered concomitant to radiotherapy and, subsequently, adjuvantly for 5-day cycles per month. Parametric and non-parametric analyses were conducted to verify the influence of several aspects of chemotherapy on the adjusted scores of each cognitive test at the two post-operative follow-ups. RESULTS: Sixty-one patients were included at T0; patients with a lower adjuvant TMZ dosage reported a better performance at the visual attention test at T1, and at the deductive reasoning test at T2. Undergoing more than 8 cycles of adjuvant therapy was slightly associated with a better performance at the long-term verbal memory tasks at T2. No other associations were found with the other cognitive tests and autonomy scales administered. CONCLUSIONS: TMZ proved to be a secure treatment with no negative side effects on cognition and on level of daily autonomy, even at the highest dosage used. This is a positive finding which enables clinicians to reassure patients about the absence of significant negative effects of TMZ on their daily life functioning. In this view, eventual cognitive changes during treatment might not be attributed to chemotherapy but to other events such as tumour relapse.

Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel.

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.

Revisiting intrathecal thiotepa: Efficacy and safety in secondary CNS malignancies.

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.

Correlation of Genetic Polymorphism of CYP3A5 to Cyclophosphamide Efficacy and Toxicity in Rhabdomyosarcoma Pediatric Egyptian Cancer Patients.

OBJECTIVES: Rhabdomyosarcoma (RMS) accounts for 50% of soft tissue sarcomas and 7% of pediatric malignancies. Cyclophosphamide (CPA) is the cornerstone of therapy and is a prodrug that is activated by the highly polymorphic drug-metabolizing enzyme CYP3A5. We aim to examine the possible CYP3A5 polymorphism association with CPA efficacy, survival outcomes, and toxicity in Egyptian pediatric RMS patients. METHODS: The three non-functional SNPs, CYP3A5*3 rs776746 (C_26201809_30), CYP3A5*6 rs10264272 (C_30203950_10), and CYP3A5*7 rs41303343 (C_32287188_10) were genotyped by real-time PCR. We conducted a cohort retrospective study of 150 pediatric RMS patients treated with CPA-based first-line treatment to analyze the association between these genotypes and CPA efficacy/toxicities in RMS patients. KEY FINDINGS: The frequency of having normal, intermediate, and poor metabolizers was 4.7%, 34%, and 61.3%, respectively. There was an association between these different phenotypes, genotypes, and CPA efficacy/toxicity. Hemorrhagic cystitis and pancytopenia were present in all patients, while nephrotoxicity incidence was 87.3%. There was a notable difference in the occurrence of hemorrhagic cystitis among CYP3A5 intermediate metabolizers *1/*3, *1/*6, and poor metabolizers *3/*3, *3/*6 with a significance level of p<0.05. Neither CYP3A5*7 polymorphism nor *6/*6 genotype was identified in our study. CONCLUSION: Our results demonstrate that CYP3A5*3 (rs776746) and CYP3A5*6 (rs10264272) have a great association with CPA efficacy and toxicity in RMS patients.

Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial.

PURPOSE: Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype. METHODS: A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m2 given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population. RESULTS: Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy. CONCLUSION: Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.

Treosulfan is a safe and effective alternative to busulfan for conditioning in adult allogeneic HSCT patients: Data from a single center.

INTRODUCTION: Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post-transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution. METHODS: Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non-relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed. RESULTS: The median follow-up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non-relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962). CONCLUSION: Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.

The protection afforded by kefir against cyclophosphamide induced testicular toxicity in rats by oxidant antioxidant and histopathological evaluations.

Cyclophosphamide (CTX) is the most commonly used effective alkylating drug in cancer treatment, but its use is restricted because its toxic side effect causes testicular toxicity. CTX disrupts the tissue redox and antioxidant balance and the resulting tissue damage causes oxidative stress. In our study based on this problem, kefir against CTX-induced oxidative stress and testicular toxicity were investigated. Rats were divided into 6 groups: control, 150 mg/kg CTX, 5 and 10 mg/kg kefir, 5 and 10 mg/kg kefir + 150 CTX. While the fermented kefirs were mixed and given to the rats for 12 days, CTX was given as a single dose on the 12th day of the experiment. Testis was scored according to spermatid density, giant cell formation, cells shed into tubules, maturation disorder, and atrophy. According to our biochemical findings, the high levels of total oxidant status (TOS), and the low levels of total antioxidant status (TAS) in the CTX group, which are oxidative stress markers, indicate the toxic effect of CTX, while the decrease in TOS levels and the increase in TAS levels in the kefir groups indicate the protective effect of kefir. In the CTX-administered group, tubules with impaired maturation and no spermatids were observed in the transverse section of the testicle, while in the kefir groups, the presence of near-normal tubule structures and tubule lumens despite CTX showed the protective effect of kefir. In our study, it was observed that kefir had a protective and curative effect on CTX-induced toxicity and oxidative stress and could be a strong protector.

Lomustine overdose in a patient with diffuse glioma: symptoms, management and outcome.

A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.

Risk factors for nausea and vomiting requiring the daily administration of 5-HT3 receptor antagonists in radiotherapy combined with temozolomide for high-grade glioma.

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT3RA) for the first 3 days. The daily administration of 5-HT3RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT3RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT3RA) and resuming 5-HT3RA group (patients who resumed 5-HT3RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT3RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT3RA group following the resumption of 5-HT3RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT3RA according to the condition of each patient.

Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice.

BACKGROUND AND AIM: Morinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo. METHODS: In vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells. RESULTS: Individual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group. CONCLUSIONS: The present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

Temozolomide-induced vitiligo-like reaction: An extremely rare phenomenon.

ABSTRACT: Temozolomide (TMZ) is an alkylating chemotherapeutic drug, often used in high-grade glioma and metastatic melanoma. Common side effects of this include myelosuppression and gastrointestinal side effects. Vitiligo-like reaction is extremely rare after TMZ. Here, we report a case of a 55-year-old patient of glioblastoma who developed vitiligo-like reaction after starting adjuvant TMZ.