• Title, Summary, Keyword: hematologic toxicity

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Gemcitabine for the Treatment of Patients with Osteosarcoma

  • Wei, Mei-Yang;Zhuang, Yan-Feng;Wang, Wan-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7159-7162
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    • 2014
  • Background: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

Pooled Analysis of Pomalidomide for Treating Patients with Multiple Myeloma

  • Sun, Jia-Jia;Zhang, Chi;Zhou, Jun;Yang, Hui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3163-3166
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    • 2015
  • Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is a new immunomodulatory drug with high in vitro potency. Immunomodulatory drugs are hypothesized to act through multiple mechanisms. Here we performed a systemic analysis to evaluate pomalidomide-based chemotherapy (pomalidomide in combination with low-dose dexamethasone) as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the efffectiveness of pomalidomide based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: For pomalidomide based regimens, 4 clinical studies which including 291 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 41.2% (120/291). Major adverse effects were hematologic toxicity, including grade 1 or 2 anemia, leucopenia and thrombocytopenia with pomalidomide based treatment. No treatment related death occurred. Conclusion: This pooled analysis suggests that pomalidomide in combination with low-dose dexamethasone is active with good tolerability in treating patients with refractory or relapsed multiple myeloma.

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

  • Ali Osman, Kaya;Suleyman, Buyukberber;Metin, Ozkan;Necati, Alkis;Alper, Sevinc;Nuriye Yildirim, Ozdemir;Suleyman, Alici;Onur, Esbah;Veli, Berk;Celalettin, Camci;Arife, Ulas;Ugur, Coskun;Mustafa, Benekli
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.463-467
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    • 2012
  • Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 $mg/m^2$ on days one and eight intravenously over 90 minutes, followed by docetaxel 75 $mg/m^2$ on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

Concurrent Chemoradiation for Unresectable Pancreatic Cancer (절제 불가능한 췌장암의 동시항암화학방사선요법)

  • Kim, Yong-Bae;Seong, Jin-Sil;Song, Si-Young;Park, Seung-Woo;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.328-333
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    • 2002
  • Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.

Efficacy of Neoadjuvant Chemotherapy and Radiotherapy for the Histology-confirmed Intracranial Germinoma - Preliminary Report (조직학적으로 확진된 두개내 배아종의 전보조화학요법 후 방사선치료의 성적 - 예비적 결과)

  • Noh, Young-Ju;Kim, Hak-Jae;Heo, Dae-Seog;Shin, Hee-Yung;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.93-99
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    • 2002
  • Purpose : We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Materials and Methods : Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP (bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. Results : The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia In 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. Conclusion : A high response rate and disease control was experienced, which was the same as observed other studies and the morbidity from chemotherapy-induced toxicity was similar. With these results, the results from adjuvant chemotherapy and involved-field radiotherapy cannot be concluded to be equal to those from extended-field radiotherapy. The long term follow-up study on later complications are required in order to draw definite conclusions on the optimal management with minimum side effects.

Effects of Concurrent Chemotherapy and Postoperative Prophylactic Paraaortic Irradiation for Cervical Cancer with Common Iliac Node Involvement (자궁경부암의 근치적 절제술 후 총장골동맥림프절 침범 시 동시항암화학치료와 예방적 대동맥주위림프절 방사선조사의 효과)

  • Han, Tae-Jin;Wu, Hong-Gyun;Kim, Hak-Jae;Ha, Sung-Whan;Kang, Soon-Beom;Song, Yong-Sang;Park, Noh-Hyun
    • Radiation Oncology Journal
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    • v.28 no.3
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    • pp.125-132
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    • 2010
  • Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.

Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma

  • Maeng, Chi Hoon;Ko, Young Hyeh;Lim, Do Hoon;Kang, Eun Suk;Choi, Joon Young;Kim, Won Seog;Kim, Seok Jin
    • Cancer Research and Treatment
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    • v.49 no.1
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    • pp.92-103
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    • 2017
  • Purpose This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas. Materials and Methods Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT. Results Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than those who showed partial response. Conclusion TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.

Intensity Modulated Whole Pelvic Radiotherapy in Patients with Cervix Cancer: Analysis of Acute Toxicity (자궁경부암 환자에서 전골반 강도변조방사선치료에 의한 급성부작용)

  • Choi, Young-Min;Lee, Hyung-Sik;Hur, Won-Joo;Cha, Moon-Seok;Kim, Hyun-Ho
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.248-254
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    • 2006
  • $\underline{Purpose}$: To evaluate acute toxicities in cervix cancer patients receiving intensity modulated whole pelvic radiation therapy (IM-WPRT). $\underline{Materials\;and\;Methods}$: Between August 2004 and April 2006, 17 patients who underwent IM-WPRT were analysed. An intravenous contrast agent was used for radiotherapy planning computed tomography (CT). The central clinical target volume (CTV) included the primary tumor, uterus, vagina, and parametrium. The nodal CTV was defined as the lymph nodes larger than 1 cm seen on CT and the contrased-enhanced pelvic vessels. The planning target volume (PTV) was the 1-cm expanded volume around the central CTV, except for a 5-mm expansion from the posterior vagina, and the nodal PTV was defined as the nodal CTV plus a 1.5 cm margin. IM-WPRT was prescribed to deliver a dose of 50 Gy to more than 95% of the PTV. Acute toxicity was assessed with common toxicity criteria up to 60 days after radiotherapy. $\underline{Results}$: Grade 1 nausea developed in 10 (58.9%) patients, and grade 1 and 2 diarrhea developed in 11 (64.7%) and 1 (5.9%) patients, respectively. No grade 3 or higher gastrointestinal toxicity was seen. Leukopenia, anemia, and thrombocytopenia occurred in 15 (88.2%). 7 (41.2%), and 2 (11.8%) patients, respectively, as hematologic toxicities. Grade 3 leukopenia developed in 2 patients who were treated with concurrent chemoradiotherapy. $\underline{Conclusion}$: IM-WPRT can be a useful treatment for cervix cancer patients with decreased severe acute toxicities and a resultant improved compliance to whole pelvic irradiation.

Feasibility Assessment of Physical Factors of Rectal Cancer Short-Course Chemoradiotherapy with Delayed Surgery

  • Koo, Jihye;Chung, Mijoo;Chung, Weon Kuu;Jin, Sunsik;Kim, Dong Wook
    • Progress in Medical Physics
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    • v.29 no.4
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    • pp.143-149
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    • 2018
  • To verify the correlations between the clinical outcomes and physical factors of short-course chemoradiotherapy (SCRT) and long-course chemoradiotherapy (LCRT) with delayed surgery in patients with rectal cancer. Seventy-two patients with rectal cancer were enrolled in this study. Nineteen patients were treated with SCRT (25 Gy, 5 fractions) by intensity-modulated radiation therapy (IMRT), and 53 patients were treated with LCRT (50.4 Gy, 28 fractions) by three-dimensional conformal radiation therapy (3DCRT). Various physical factors for the target and organs at risk (OARs) were calculated to compare the clinical outcomes. The organ equivalent dose (OED) and lifetime attributable risk (LAR) of bowels and bladders were similar between the SCRT and LCRT groups, whereas the values of femurs were higher in the LCRT group. The equivalent uniform dose and normal tissue complication probability were higher in the LCRT than the SCRT group for most organs. Treatment complications, including anastomotic leakage, bowel adhesion, and hematologic toxicity, were not significantly different between SCRT and LCRT groups. CIs were $0.84{\pm}0.2$ and $0.61{\pm}0.1$ for SCRT and LCRT, respectively. The CVIs were $1.07{\pm}0.0$ and $1.10{\pm}0.1$, and the HIs were $0.09{\pm}0.0$ and $0.11{\pm}0.1$ for SCRT and LCRT, respectively. The sphincter-saving rates were 89.5% and 94.3% for SCRT and LCRT, respectively. The complete pathologic remission rates were 21.1% and 13.2%, and the down-staging rates were 47.4% and 26.4% for SCRT and LCRT, respectively. SCRT with IMRT is comparable to conventional LCRT in both physical indexes and clinical outcome. The preoperative SCRT, compensated by IMRT, is an effective and safe modality.

Two Cases of Severe Pancytopenia Associated with Low-Dose Methotrexate Therapy in Patients with Chronic Kidney Disease and Rheumatoid Arthritis (류마티스 관절염을 가진 만성신질환 환자에서 저용량 methotrexate 투여 후 발생한 중증 범혈구 감소증 2예)

  • Kim, Hong-Ik;Lee, Woo-Hyun;Oh, Jang-Seok;Hong, Hyo-Rim;Lee, In-Hee
    • Yeungnam University Journal of Medicine
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    • v.28 no.1
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    • pp.60-69
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    • 2011
  • Due to its efficacy and tolerability, low dose oral methotrexate (MTX) therapy has been widely used for treatment of rheumatoid arthritis (RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease (CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240 mg) and 4 years (cumulative dose 1,320 mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells (RECs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included REC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

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