• Title, Summary, Keyword: hematologic toxicity

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Chemoradiation Related Acute Morbidity in Carcinoma Cervix and Correlation with Hematologic Toxicity: A South Indian Prospective Study

  • Kumaran, Aswathy;Guruvare, Shyamala;Sharan, Krishna;Rai, Lavanya;Hebbar, Shripad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4483-4486
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    • 2014
  • Purpose: To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. Materials and Methods: A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Results: Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in $3^{rd}$ and $5^{th}$ week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Conclusions: Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.

GSTT1 null and MPO -463G>A Polymorphisms and Carboplatin Toxicity in an Indian Population

  • Bag, Arundhati;Pant, Nirdosh Kumar;Jeena, Lalit Mohan;Bag, Niladri;Jyala, Narayan Singh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4739-4742
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    • 2013
  • Carboplatin, a second generation platinum drug, is widely used to treat different types of cancers. However, myelosuppression remains a major consideration in its use. Genetic polymorphisms of enzymes involved in drug disposition can influence therapeutic outcome. The homozygous null deletion of phase II metabolic gene GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with carboplatin toxicity. Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects. We here investigated the null polymorphism of GSTT1, and the -463G>A promoter polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin toxicity in a population of northern India. Cancer patients who were treated with carboplatin, and developed toxicity was considered. The study group comprised of 10 patients who developed therapy- related adverse effects. Peripheral blood was taken from patients for DNA isolation. GSTT1 null genotype was determined by conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP. Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4 toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI) toxicity. Remaining 5 individuals developed GI toxicity but no hematological toxicity. While GG homozygous of MPO was present in majority of patients having hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was present in 4 patients who did not have any hematological toxicity. Thus variant A allele of MPO -463G>A may be related to lower hematological toxicity. These preliminary data, however, are required to be confirmed in larger studies along with other relevant polymorphisms.

Fertility preservation for patients with hematologic malignancies: The Korean Society for Fertility Preservation clinical guidelines

  • Lee, Dong-Yun;Kim, Seul Ki;Kim, Miran;Hwang, Kyung Joo;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.44 no.4
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    • pp.187-192
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    • 2017
  • Although the survival rate of hematologic malignancies in young patients is very high, cytotoxic therapies such as chemotherapy and total body irradiation therapy can significantly reduce a patient's reproductive capacity and cause irreversible infertility. Early ovarian failure also commonly occurs following additional cancer treatment, bone marrow transplantation, or autologous transplantation. Because the risk of early ovarian failure depends on the patient's circumstances, patients with a hematologic malignancy must consult health professionals regarding fertility preservation before undergoing treatments that can potentially damage their ovaries. While it is widely known that early menopause commonly occurs following breast cancer treatment, there is a lack of reliable study results regarding fertility preservation during hematologic malignancy treatment. Therefore, an in-depth discussion between patients and health professionals about the pros and cons of the various options for fertility preservation is necessary. In this study, we review germ cell toxicity, which occurs during the treatment of hematologic malignancies, and propose guidelines for fertility preservation in younger patients with hematologic malignancies.

Effect of Pyridoxine on Rifampicin Toxicity

  • Yun, Yeo-Pyo;Kim, Koan-Hoi;Kim, Hack-Seang;Chung, Jin-Ho
    • Archives of Pharmacal Research
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    • v.14 no.1
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    • pp.73-77
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    • 1991
  • The effects of pyridoxine (PN) on rifampicin (RMF) toxicity were investigated by both in vivo and in vitro methods. RMF (30 mg/kg) was injected intraperitoneally and PN(150 mg/kg) was administered orally to rats for 10 consecutive days. After treatment, clinical chemistry and hematologic profiles were measured. RMF and PN plus RMF did not show any adverse effects at this in vivo experimental condition. Thymidine incorporations of mice bone marrow cells were examined in vitro. RMF showed a decrease in thymidine uptake in a dose-dependent manner, but PN showed a reversal of the thymidine uptake suppression caused by RMF (p<0.01). On the other hand, PN showed a decrease in thymidine uptake at a high concentration level.

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Concurrent Weekly Cisplatin Versus Triweekly Cisplatin with Radiotherapy in the Treatment of Cervical Cancer: A Meta-analysis Result

  • Hu, Yan;Cai, Zhi-Qiang;Su, Xiao-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4301-4304
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    • 2012
  • Aims: To evaluate the adverse effect and survival outcome of weekly and triweekly cisplatin with radiotherapy in treatment of cervical cancer. Methods: After an extensive literature search between 1995-2011, we analyzed 7 studies to compare weekly cisplatin and triweekly cisplatin combined radiotherapy. Results: Our analysis established that weekly cisplatin has a lower risk of hematologic toxicity than triweekly cisplatin with concurrent radiotherapy in the treatment of cervical cancer. However, there were no differences in progression free survival and overall survival between weekly cisplatin and triweekly cisplatin (p>0.05). Conclusions: Weekly cisplatin combined with concurrent radiation has lower risk in hematologic toxicity than triweekly cisplatin, but does not improve survival. Triweekly cisplatin treatment has longer intervals and is therefore more convenient. Clinicians and patients can choose either weekly cisplatin or triweekly cisplatin combined radiotherapy for cervical cancer.

"Sandwich" Chemotherapy (CT) with Radiotherapy (RT) Improves Outcomes in Patients with Stage IE/IIE Extranodal Natural Killer (NK)/T-cell Lymphomas

  • Zhang, Jing;Zhu, Meng-Yuan;Wang, Liang;Wang, Hua;Wang, Wei-Da;Geng, Qi-Rong;Lu, Yue
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4061-4066
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    • 2013
  • The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.

Clinical Observation and Prognostic Analysis of Pemetrexed plus Platinum as First-line Treatment in Patients with Advanced Non-small Cell Lung Cancer

  • Wang, Ji-Ying;Cai, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6267-6271
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    • 2013
  • Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

The Toxicity and Preliminary Clinical Outcomes of Low-Dose Weekly Cisplatin-Based Concurrent Chemoradiotherapy (두경부암에서 저용량 Cisplatin 기반 매주 요법의 항암방사선 동시치료의 독성과 예비 임상 결과)

  • Kim, Tae-Yong;Kim, Kyoung-Ju;Kim, Ki-Hwan;Kim, Ji-Eun;Park, Sun-Won;Oh, So-Won;Jung, Young-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.27 no.1
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    • pp.47-53
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    • 2011
  • Purpose : Concurrent chemoradiotherapy(CCRT) with 3 weekly cisplatin is the standard treatment of locally advanced head and neck cancer(HNC). The aim is to evaluate the efficacy and toxicities of low-dose weekly cisplatin-based CCRT, which was devised to reduce the toxicity of CCRT. Method : We retrospectively analyzed HNC patients who received low-dose weekly cisplatin-based CCRT between 2008 and 2010. Cisplatin 35mg/$m^2$ was weekly given to all patients during radiotherapy. The efficacy was evaluated by the degree of clinical response, treatment failure and survival. The toxicity was evaluated by hematologic toxicities and oral mucositis. Results : A total of 27 patients were analyzed and median age was 59(range 31-81). The ratio of administered dose of radiotherapy and cisplatin to planned dose were 0.98 and 0.93, respectively. Complete remission and partial remission were 73% and 23%, respectively. Treatment failure was observed in 8(30%) patients. 1-year survival rate and 1-year disease free survival rate were 82% and 59%, respectively. Overall survival and progression-free survival did not reach median time. Grade 3/4 anemia, neutropenia, thrombocytopenia and oral mucositis were observed in 11%, 19%, 7% and 32% of patients, respectively. In terms of administered cycles, however, only 1-3% of grade 3/4 hematologic toxicities occurred among total 190 cycles. Severe oral mucositis were statistically associated with old age(p=0.003). Treatment failure had no statistical relation with age, pathology, primary site and stage. Conclusion : Low-dose weekly cisplatin-based CCRT seemed to deliver enough dose of cisplatin and to show low drop-out rate and good efficacy with low hematologic toxicities.

Conventional Radiotherapy with Concurrent Weekly Cisplatin in Locally Advanced Head and Neck Cancers of Squamous Cell Origin - a Single Institution Experience

  • Dimri, Kislay;Pandey, Awadhesh Kumar;Trehan, Romeeta;Rai, Bhavana;Kumar, Anup
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6883-6888
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    • 2013
  • Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 $mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at $35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35 $mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice

  • Titlow, William B.;Lee, Chul-Hoon;Ryou, Chongsuk
    • Journal of Microbiology and Biotechnology
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    • v.23 no.7
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    • pp.1015-1022
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    • 2013
  • We recently showed that polylysine, the polymer of lysines, retains anti-prion activity. Although the effectiveness of prion inhibition by polylysine was demonstrated with the regimen tolerated in mice, a determination of quantitative polylysine toxicity is necessary to precisely address the in vivo toxicity level of polylysine. In this communication, we report the results of body weight monitoring and hematologic tests performed in CD-1 mice that received two different tolerable dosages of polylysine for an either 5-day or 4-week period. We found that there was no significant alteration in overall serum chemistry, blood cell count, and body weight gain compared with controls. The only notable quantitative change with statistical significance was the decrease of platelet numbers in mice subchronically administered with polylysine. Our results suggest that polylysine is harmless in mice if administered for a short period, but administrations of polylysine in mice may require considerate attention for safety in future investigations as mice chronically receive tolerable doses of polylysine.