• Title/Summary/Keyword: Bone marrow suppression

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STUDIES ON ANTI-ORAL CANCER ACTIVITIES OF MEDICINAL PLANT EXTRACTS (구강암에 대한 약용식물 추출물의 항암효과에 관한 연구)

  • Lee, Young-Hoon;Kim, Yeo-Gab;Kim, Jung-Hee
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.1
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    • pp.53-58
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    • 2000
  • Treatment of oral cancers with chemotherapeutic agents are evaluated as an effective method for remission to reduce cancer proliferation nowadays. But, minimization of side-effects such as bone marrow suppression, gastrointestinal toxicity and renal damage is another problem to be solved. Thus, a possible approach to develop a clinically applicable chemotherapeutic agents is to screen anticancer activity among traditional medicinal plants which have been used for thousands of years with very low side-effects in orient. In this study we focused on screening anti-oral cancer activities among 14 traditional medicinal plant extracts that revealed anticancer activities on other solid tumors. The results were as follow : 1. Methanol extract of Lepidium apetalum showed the highest anti-oral cancer activity against A253 cells. At concentration of $4{\mu}g/ml$, the cell viability was 48% under our experimental condition. $IC_{50}$ value obtained was $4{\mu}g/ml$. 2. Methanol extract of Coptis japonica and Solanum nigrum were effective on KB cells. Cell viability observed were 62% and 67% at concentration of $4{\mu}g/ml$, and $IC_{50}$ values were $12{\mu}g/ml$ and $10{\mu}g/ml$ respectively. 3. When the methanol extract of Lonicera caerule was combined with $2{\mu}g/ml$ of cisplatin, the anticancer activity was synergistically increased. One hundred ${\mu}g/ml$ of Lonicera caerule showed 92%(alone) or 59%(combined with cisplatin) cell viabilities. $IC_{50}$ value of Lonicera caerule extract against KB cells was reduced from $301{\mu}g/ml$ to $126{\mu}g/ml$ when combined with $2{\mu}g/ml$ of cisplatin. 4. Medicinal plant extracts effective on both A253 and KB cells were Coptis japonica, Lepidium apetalum, Solanum nigrum, Caesalpiniae Lignum, Curcuma aromatica.

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A literal study of anti-tumor effects of chunghwangsan for leukemia (청황산(靑黃散)의 백혈병(白血病)에 대(對)한 항종양효능(抗腫瘍效能) 연구(硏究))

  • Park, Jong-hak;Son, Chang-gyu;Cho, Chong-kwan
    • Journal of Haehwa Medicine
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    • v.10 no.2
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    • pp.83-89
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    • 2002
  • In the literatual study of anti-tumor effects of chunghwangsan for leukemia, the results were as follows. 1. Chunghwangsan is composed of Indigo naturalis and Realgar. The composing rate is 9 : 1 and it is made into capsule or piece. The basic administration is 0.3g per day and could increase the quantity each day. 2. The effects of Chunghwangsan is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer are. So it can be used to treat AML, CML and lymphoma. 3. The anticancer component of Indigo naturalis is indirubin which has the effects of suppression the transplanted tumor, activating the phagocyte of macrophage, promoting the maturation of myeloblast to improve cure rate of CML. The anticancer component of Realgar is $As_2O_3$ which has the direct cellular toxicity for leukemia cell. 4. In viewpoints of oriental medicine, leukemia is malignant myeloid neoplasia in which pathogen invade to shaoyin(少陰). So Chunghwangsan which is expelling toxin and colling, colling blood to detumescence, drying wetness and anticancer is effective to leukemia. 5. In clinical reports, Chunghwangsan is often used in CML, and also used in AML, lymphoma and so on. 6. Chunghwangsan is cool-natured, so we must carefully pay attention to pregnant women and hematsdthenic patients. The main side effects are nausea, bone marrow pain, diarrhea, polydefecation, hematokezia and purpora. We sometimes take invigorating stomach medicine to prevent the side effects. 7. If we continuously develop Chunghwangsan and therapy for leukemia with syndrome differentiation. we can improve the response and cure rate for leukemia in the future.

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Delayed Elimination After High-dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma (소아 급성림프모구백혈병 및 비호지킨림프종 환자에서 고용량 methotrexate 투여 후 배설지연)

  • Yoon, Hye Won;Ree, Yoon Sun;Song, Hyo Sook;Kim, Jae Song;Son, Eun Sun
    • Korean Journal of Clinical Pharmacy
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    • v.29 no.2
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    • pp.101-108
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    • 2019
  • Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received $5g/m^2$ MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or $150{\mu}M$ MTX at 24 hours, and 2 or $5{\mu}M$ at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > $100{\mu}M$ showed higher percentage than group with MTX concentration < $100{\mu}M$ (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at $150{\mu}M$ MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at $2{\mu}M$, p = 0.024 at $5{\mu}M$). Conclusions: MTX concentrations greater than $100{\mu}M$ show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.

Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells

  • Eun-Ji Choi;Bon-Kwan Koo;Eun-Hye Hur;Ju Hyun Moon;Ji Yun Kim;Han-Seung Park;Yunsuk Choi;Kyoo-Hyung Lee;Jung-Hee Lee;Eun Kyung Choi;Je-Hwan Lee
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.319-329
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    • 2023
  • Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

A New Radiation-Shielding Device for Restraining Veterinary Patients

  • Songyi Kim;Minju Lee;Miju Oh;Yooyoung Lee;Jiyoung Ban;Jiwoon Park;Sojin Kim;Uhjin Kim;Jaepung Han;Dongwoo Chang
    • Journal of Veterinary Clinics
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    • v.40 no.6
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    • pp.429-437
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    • 2023
  • In veterinary medicine, most radiographic images are obtained by restraining patients, inevitably exposing the restrainer to secondary scattered radiation. Radiation exposure can result in stochastic reactions such as cancer and genetic effects, as well as deterministic reactions such as skin burns, cataracts, and bone marrow suppression. Radiation-shielding equipment, including aprons, thyroid shields, eyewear, and gloves, can reduce radiation exposure. However, the risk of radiation exposure to the upper arms, face, and back remains, and lead aprons and thyroid shields are heavy, restricting movement. We designed a new radiation-shielding system and compared its shielding ability with those of conventional radiation-shielding systems. We hypothesized that the new shielding system would have a wider radiation-shielding range and similar shielding ability. The radiation exposure dose differed significantly between the conventional and new shielding systems in the forehead, chin, and bilateral upper arm areas (p < 0.001). When both systems were used together, the radiation-shielding ability was better than when only one system was used at all anatomical locations (p < 0.01). This study suggests that the new radiation-shielding system is essential and convenient for veterinary radiation workers because it is a step closer to radiation safety in veterinary radiography.

Effect of Water Extract of Aloe in RANKL-induced Osteoclast Differentiation (파골세포 분화에 미치는 노회(蘆會) 추출물의 효과)

  • Lee, Jeong-Hugh;Lee, Myeung-Su;Chae, Soo-Uk;Kim, Ha-Young;Moon, Seo-Young;Jeon, Byung-Hoon;Cho, Hae-Joong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.6
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    • pp.1008-1013
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    • 2011
  • Osteoporosis is the leading underlying cause of fractures, particularly in postmenopausal women, due to the loss of estrogen-mediated suppression of bone resorption. More than 50% of adults 50 years of age or older are estimated to have osteoporosis. Osteoclast which is main target for treatment of osteoporosis is originated from hematopoietic cell line. Aloe has been widely used in worldwide country as a coadjuvant medicine. Extracts of the leaves of Aloe have been used in condition to improve dermatologic problem such as seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus and has been known to exert anti-inflammatory, anti-oxidant and anti-tumor effects. However, despite the popularity of aloe as a plant food supplements, the evaluation of its efficacy as a possible therapeutic option for osteoporosis remains scarce. Thus, we evaluated the effect of Aloe on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Here we found that Aloe significantly inhibited osteoclast differentiation induced by RANKL. Aloe suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Aloe significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Aloe greatly inhibited the protein expression of c-fos and NFATc1. Taken together, our results suggested that Aloe may be useful tool for treatment of osteoporosis by inhibition of osteoclast differentiation.

Quantitative Assessment and Ligament Traceability of Volume Isotropic Turbo Spin Echo Acquisition (VISTA) Ankle Magnetic Resonance Imaging: Fat Suppression versus without Fat Suppression (발목관절 VISTA 자기공명영상에서 정량평가와 인대의 Traceability: 지방억제 대비 지방억제기법)

  • Cho, Kyung Eun;Yoon, Choon-Sik;Song, Ho-Taek;Lee, Young Han;Lim, Daekeon;Suh, Jin-Suck;Kim, Sungjun
    • Investigative Magnetic Resonance Imaging
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    • v.17 no.2
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    • pp.110-122
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    • 2013
  • Purpose : To compare the image quality and ligament traceability in ankle images obtained using Volume Isotropic Turbo Spin Echo Acquisition (VISTA) MRI with and without fat suppression. Materials and Methods: The signal-to-noise ratios (SNRs) in images from a phantom and from the ankle of a volunteer were compared. Ten ankles from 10 non-symptomatic volunteers were imaged for comparisons of contrast ratio (CR) and ligament traceability. All examinations were performed using VISTA sequences with and without fat suppression on a 3T MRI scanner. The SNRs were obtained from images with subjects and without subjects (noise-only). Contrast ratios from images of the 10 ankles were acquired between fluid and tendon (F-T), F-cartilage (C), F-ligament (L), fat (f)-T, f-C and f-L. Two musculoskeletal radiologists independently scored the traceability of 7 ligaments, in sagittal, axial and coronal images respectively, based on a 4-point scale (1 as not traceable through 4 as clearly traceable). The Wilcoxon signed-rank test was used to compare the CR. Fisher's exact test and Pearson's chi-squared test were used to compare the ligament traceability. Results: The SNRs did not differ significantly between the two sequences except in bone marrow. VISTA SPAIR showed the higher CR only in F-T (p = 0.04), whereas VISTA showed higher CR in f-T (p = 0.005), f-C (p = 0.005) and f-L (p = 0.005). The calcaneofibular ligament traceability with VISTA was superior to that obtained with VISTA SPAIR (p < 0.05) in all planes. Conclusion: VISTA showed significant superiority to VISTA SPAIR in tracing CFL due to the superior CR between fat and ligament.

Comparison of the Result of Radiation Alone and Chemoradiation in Cervical Cancer (자궁 경부암에서 방사선 단독치료와 방사선 및 화학요법 병행치료의 비교)

  • Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.191-198
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    • 1995
  • Purpose: This analysis was to compare the result of radiation alone and chemoradiation in cervical cancer in terms of response, survival, failure, and complication. Materials and Methods: A retrospective analysis of 135 cervical cancer patients treated with definitive radiotherapy from November 1985 to December 1991 was performed. Fifty-six patients were treated with radiation alone and 79 patients were treated with cisplatin-based chemotherapy plus radiation. Follow-up period ranged from 5 to 105 months with a median 47 months. According to the FIGO classification, the patients were subdivided into 18 $(13.3\%)$ stage IB, 7 $(5.2\%)$ stage IIA, 97 $(71.9\%)$ stage IIB, and 9 $(6.7\%)$ stage IIIB. Results: A complete response was noted in 51 patients $(91.1\%)$ of the radiation alone group, and 68 patients $(86.1\%)$ of the chemoradiation group. There was no statistical difference in complete response rate between the two groups. Overall survival rate at 5 years was $73.3\%$. According to stage, overall survival rates at 5 years were $88.9\%$ in stage IB, $85.7\%$ in stage IIA, $73.8\%$ in stage IIB, and $37.5\%$ in stage IIIB, respectively. According to treatment modality, overall survival rates at 5 years were $81.9\%$ in the radiation alone group, $67.0\%$ in the chemoradiation group (p=0.22). Disease-free survival rate at 5 years were $70.4\%$ in the radiation alone group. $68.5\%$ in the chemoradiation group (p=0.85) Locoregional control rates at 5 years were $76.1\%$ in the radiation alone group, $73.8\%$ In the chemoradiation group (p=0.70). Distant disease-free survival rates at 5 years were $83.9\%$ in the radiation alone group, $90.3\%$ in the chemoradiation group (p=0.59). Treatment-related bone marrow suppressions were noted in 3 $(5.4\%)$ patients of the radiation alone group, 14 patients $(17.7\%)$ of the chemoradiation group (p(0.05). Grade 2 vesical complications were noted in 14 patients of the radiation alone group. and 10 Patients of the chemoradiation group. Grade 2 rectal complications were noted in 2 patients of the radiation alone group, and 3 Patients of the chemoradiation group. One case of rectal perforation was noted in the chemoradiation group, and grade 2 small bowel obstructions were noted in 2 patients of the radiation alone group. There were no statistical differences in the incidence of vesicar, rectal, and small bowel complicaions between the two groups. Conclusion: No statistical difference was found between the radiation alone group and the chemoradiation group in terms of response, survival, and failure. but the incidence of bone marrow suppression was higher in the chemoradiation group.

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Study of Pemetrexed-based Chemotherapy for Patients with Locally Advanced or Metastatic Cancers

  • Qian, Ting;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4791-4795
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    • 2015
  • Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapy in treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy. Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer, 19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advanced gallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer in Jiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated with pemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results: For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligible for inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD, progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexed based regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made use of this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 of them got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients used this regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last 14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among 17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-line treatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients could not be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%. Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as first-line treatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patients accepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD. Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-line treatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment. Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment, the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed based regimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bone marrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers such as breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify the results.

Phase II Study on Dose Escalating Schedule of Paclitaxel Concurrent with Radiotherapy in Treating Patients with Locally Advanced Non-small Cell Lung Cancer

  • Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Chen, Jue;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1699-1702
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    • 2014
  • Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.