• Title/Summary/Keyword: Toxicity Endpoints

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Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

  • Liang, Yong;Bu, Jun-Guo;Cheng, Jin-ling;Gao, Wei-Wei;Xu, Yao-Can;Feng, Jian;Chen, Bo-Yu;Liang, Wei-Chao;Chen, Ke-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6011-6017
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    • 2015
  • Purpose: To investigate the efficacy and safety of selective radiotherapy after distant metastasis of nasopharyngeal carcinoma (NPC) treated with dose-dense cisplatin plus fluorouracil. Materials and Methods: Eligible patients were randomly assigned to a study group treated with dose-dense cisplatin plus fluorouracil following selective radiotherapy and a control group receiving traditional cisplatin plus fluorouracil following selective radiotherapy according to a 1:1 distribution using a digital random table method. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, relapse or progression rate in the radiation field and treatment toxicity. Results: Of 52 patients in the study group, 20 cases underwent radiotherapy., while in the control group of 51 patients, 16 underwent radiotherapy. The median PFS, median OS, survival rates in 1, 2 and 3 years in study and control group were 20.9 vs 12.7months, 28.3 vs 18.8months, 85.2%vs 65.9%, 62.2% vs 18.3%, and 36.6%vs 5.2% (p values of 0.00, 0.00, 0.04, 0.00 and 0.00, respectively). Subgroup analysis showed that the median OS and survival rates of 1, 2, 3 years for patients undergoing radiotherapy in the study group better than that in control group( 43.2vs24.1 months, 94.1% vs 86.7%, 82.4% vs 43.3%, 64.7% vs 17.3%, (p=0.00, 0.57, 0.04 and 0.01, respectively). The complete response rate, objective response rate after chemotherapy and three months after radiotherapy, relapse or progression rate in radiation field in study group and in control group were 19.2% vs 3.9%, 86.5% vs 56.9%, 85% vs 50%, 95% vs 81.3% and 41.3% vs 66.7% (p =0.03, 0.00, 0.03,0.30, 0.01 respectively). The grade 3-4 acute adverse reactions in the study group were significantly higher than in the control group (53.8% vs 9.8%, p=0.00). Conclusions: The survival of patients benefits from selective radiotherapy after distant metastasis of NPC treated with dose-dense cisplatin plus fluorouracil.

Toxic effects of antifouling agents (diuron and irgarol) on fertilization and normal embryogenesis rates in the sea urchin (Mesocentrotus nudus) (둥근성게(Mesocentrotus nudus)의 수정 및 배아 발생률에 미치는 신방오도료(Diuron, Irgarol)의 독성영향)

  • Hwang, Un-Ki;Lee, Ju-Wook;Park, Yun-Ho;Heo, Seung;Choi, Hoon
    • Korean Journal of Environmental Biology
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    • v.38 no.2
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    • pp.207-215
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    • 2020
  • Toxic assessment of antifouling agents (diuron and irgarol) was conducted using the fertilization and the normal embryogenesis rates of the sea urchin, Mesocentrotus nudus. Bioassessment began with male and female reproductive cell induction. White or cream-colored male gametes(sperm) and yellow or orange-colored female gametes (eggs) were acquired and fully washed, separately. Then, the fertilization and normal embryogenesis rates were measured after 10 min and 48 h of exposure to the toxicants, respectively. The fertilization and embryo development rates were greater than 90% in the control, validating the suitability of both endpoints. The normal embryogenesis rates were significantly decreased with increasing concentrations of diuron and irgarol, but no changes in the fertilization rates were observed in concentrations ranging from 0 to 40 mg L-1. The EC50 values of diuron and irgarol for the normal embryogenesis rates were 20.07 mg L-1 and 22.45 mg L-1, respectively. The no observed effect concentrations (NOEC) were <1.25 mg L-1 and the lowest observed effect concentrations (LOEC) were 1.25 mg L-1 and 2.5 mg L-1, respectively. From these results, concentrations of diuron and irgarol over 1.25 mg L-1 and 2.5 mg L-1, respectively, can be considered to have toxic effects on invertebrates, including M. nudus. The ecotoxicological bioassay in this study using the noted fertilization and normal embryogenesis rates of M. nudus can be used as baseline data for the continued establishment of environmental quality standards for the effects of antifouling agents(especially diuron and irgarol) in a marine environment.

Once vs. Twice Daily Thoracic Irradiation in Limited Stage Small Cell Lung Cancer (국한성 병기 소세포폐암의 방사선치료시 분할 조사방식에 따른 치료성적)

  • Kim, Jun-Sang;Kim, Jae-Sung;Kim, Ju-Ock;Kim, Sun-Young;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.291-301
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    • 1998
  • Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

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