Cancer Research and Treatment

Case Report

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors of the Stomach: Report of Three Cases: Ji Seon Oh, Jae-Lyun Lee, Mi-Jung Kim, Min-Hee Ryu, Heung Moon Chang, Tae Won Kim, Se Jin Jang, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Yoon-Koo Kang; Cancer Res Treat. 2006;38(3):178-183. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.178

Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

Citations

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Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor
Dong-Hoe Koo, Min-Hee Ryu, Kyoung-Mee Kim, Han-Kwang Yang, Akira Sawaki, Seiichi Hirota, Jie Zheng, Bo Zhang, Chin-Yuan Tzen, Chun-Nan Yeh, Toshirou Nishida, Lin Shen, Li-Tzong Chen, Yoon-Koo Kang
Cancer Research and Treatment.2016; 48(4): 1155. CrossRef
Correlation between Computed Tomography and Pathological Findings of Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate
Ki Choon Sim, Beom Jin Park, Na Yeon Han, Deuk Jae Sung, Min Ju Kim, Sung Bum Cho, Hyun Kwon Ha, Hyoung Rae Kim
Journal of the Korean Society of Radiology.2014; 71(5): 239. CrossRef
Diagnosis and Treatment of Gastrointestinal Stromal Tumor
Yoon-Koo Kang, Dong Hoe Koo
Korean Journal of Medicine.2013; 85(4): 341. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Hye Jin Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Cancer Research and Treatment.2012; 44(2): 85. CrossRef
Efficacy of Imatinib Mesylate Neoadjuvant Treatment for a Locally Advanced Rectal Gastrointestinal Stromal Tumor
Kyu Jong Yoon, Nam Kyu Kim, Kang Young Lee, Byung Soh Min, Hyuk Hur, Jeonghyun Kang, Sarah Lee
Journal of the Korean Society of Coloproctology.2011; 27(3): 147. CrossRef
Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang, Kyoung-Mee Kim, Taesung Sohn, Dongil Choi, Hye Jin Kang, Min-Hee Ryu, Woo Ho Kim, Han-Kwang Yang
Journal of Korean Medical Science.2010; 25(11): 1543. CrossRef
Clinical Practice Guideline for Adequate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea
Yoon-Koo Kang
Journal of the Korean Medical Association.2007; 50(9): 830. CrossRef

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Original Articles

Optimal Timing for the Administration of Capecitabine with Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Young Ju Noh, Won Sik Choi, Jong Hoon Kim, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jung Eun Lee, Eun Kyung Choi; Cancer Res Treat. 2006;38(1):30-34. Published online February 28, 2006; DOI: https://doi.org/10.4143/crt.2006.38.1.30

Abstract PDF PubReader ePub

Purpose

Capecitabine is an oral fluoropyrimidine carbamate and it is known as an effective radiosensitizer. Capecitabine and its metabolite reach their peak concentration in the plasma at 1~2 hours after a single oral administration of capecitabine and the levels fall rapidly thereafter. To verify the radiosensitizing effect of capecitabine that is based on such pharmacokinetic characteristics, we performed a retrospective analysis on the optimal timing of capecitabine administration with performing preoperative chemoradiation for locally advanced rectal cancer.

Materials and Methods

Among 171 patients who were treated with preoperative radiotherapy and concurrent capecitabine administration for rectal cancer, 56 patients were administered capecitabine at 1~2 hours before radiotherapy (group A), and at other time in the other 115 patients (group B). Total mesorectal excision was done at 4 to 6 weeks after the completion of chemoradiation. The radiosensitizing effect of capecitabine was evaluated on the basis of the pathological response.

Results

Complete pathological regression of the primary tumor was observed in 12 patients (21.4%) for group A and in 11 patients (9.6%) for group B (p=0.031). Residual disease less than 0.5 cm (a good response) was observed in 19 patients (33.9%) for group A and in 23 patients (20.0%) for group B (p=0.038). On multivariate analysis, the capecitabine ingestion time showed marginal significance.

Conclusion

When performing preoperative chemoradiation for locally advanced rectal cancer, the radiosensitizing effect of capecitabine was enhanced when it was administered 1 hour before radiotherapy.

Citations

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Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer
R Clifford, N Govindarajah, J L Parsons, S Gollins, N P West, D Vimalachandran
British Journal of Surgery.2018; 105(12): 1553. CrossRef

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Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy: Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Jung Shin Lee, Yoon-Koo Kang; Cancer Res Treat. 2005;37(4):201-207. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.201

Abstract PDF PubReader ePub

Purpose

Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.

Materials and Methods

A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m² IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.

Results

A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.

Conclusion

Docetaxel, 75 mg/m², is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Citations

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Comparison of adverse events following injection of original or generic docetaxel for the treatment of breast cancer
Nao Tagawa, Erika Sugiyama, Masataka Tajima, Yasutsuna Sasaki, Seigo Nakamura, Hiromi Okuyama, Hisanori Shimizu, Vilasinee Hirunpanich Sato, Tadanori Sasaki, Hitoshi Sato
Cancer Chemotherapy and Pharmacology.2017; 80(4): 841. CrossRef
Efficacy and Safety of Trastuzumab-based Therapy in Combination with Different Chemotherapeutic Regimens in Advanced Esophagogastric Cancer – a Single Cancer-center Experience
Georg-Martin Haag, Leonidas Apostolidis, Dirk Jaeger
Tumori Journal.2014; 100(3): 237. CrossRef
Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors
Nicolas Isambert, Gilles Freyer, Sylvie Zanetta, Benoît You, Pierre Fumoleau, Claire Falandry, Laure Favier, Sylvie Assadourian, Karen Soussan-Lazard, Samira Ziti-Ljajic, Veronique Trillet-Lenoir
Clinical Cancer Research.2012; 18(6): 1743. CrossRef
A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy
Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Minsun Kim, Young Joo Chun, Jung Shin Lee, Yoon-Koo Kang
Cancer Chemotherapy and Pharmacology.2008; 61(4): 631. CrossRef

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Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer: In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim; Cancer Res Treat. 2004;36(6):360-366. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.360

Abstract PDF PubReader ePub: Purpose
The aim of this study was to evaluate the responsiveness to CPT-11 with respect to hMLH1 and hMSH2 protein expressions in primary colorectal tumors.
Materials and Methods
91 patients with colorectal cancer treated having undergone surgery and postoperative CPT-11-based adjuvant chemotherapy, between 1997 and 2002, were prospectively recruited. Tumor samples were immunohistochemically analyzed for the expressions of hMLH1, hMSH2, p53 and CEA proteins.
Results
Of the 91 tumors, 6 (6.6%) and 4 (4.4%) showed loss of hMLH1 and hMSH2 protein expressions, respectively. The response rate of patients with tumors not expressing either hMLH1 or hMSH2 was higher than that of those expressing either of these proteins (p=0.026). Patients with tumors not expressing hMLH1 showed a significantly better response to CPT-11 (p=0.04). The responsiveness was not associated with the expressions of hMSH2, p53 or CEA. There were no correlations between drug toxicity and the expressions of hMLH1, hMSH2 or p53. The overall survival was better in patients responsive to CPT-11-based chemotherapy compared to non-responders.
Conclusion
The immunohistochemical determination of loss of hMLH1 and hMSH2 expressions may be used in determining the responsiveness to CPT-11-based chemotherapy. Our results suggest that hMLH1 protein expression may be a predictor for CPT-11 responsiveness in patients with colorectal cancer.

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Prospective Phase II Study of Preoperative Chemoradiation with Capecitabine in Locally Advanced Rectal Cancer: Jin-hong Park, Jong Hoon Kim, Seung Do Ahn, Sang-wook Lee, Seong Soo Shin, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Yoon-Koo Kang, Tae Won Kim, Heung Moon Chang, Min Hee Ryu, Eun Kyung Choi; Cancer Res Treat. 2004;36(6):354-359. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.354

Abstract PDF PubReader ePub

Purpose

Capecitabine is an attractive oral chemotherapeutic agent that has a radiosensitizing effect and tumor-selectivity. This study was performed to evaluate the efficacy and toxicity of preoperative chemoradiation therapy, when used with oral capecitabine, for locally advanced rectal cancer.

Materials and Methods

A prospective phase II trial of preoperative chemoradiation for locally advanced adenocarcinomas of the lower two-thirds of the rectum was conducted. A radiation dose of 50 Gy over five weeks and a daily dose of 1650 mg/m² capecitabine in two potions was administered during the entire course of radiation therapy. Surgery was performed with standardized total mesorectal excision four to six weeks after completion of the chemoradiation.

Results

Between January 2002 and September 2003, 61 patients were enrolled onto this prospective phase II trial. The pretreatment clinical stages were T3 in 64% (n=39), T4 in 36% (n=22) and N1-2 in 82% (n=50) of these patients. Fifty-six (92%) patients completed the chemoradiation as initially planned and a complete resection performed in 58 (95%). Down-staging was observed in 45 patients (74%) and a pathologic complete response in 6 (10%). Among the 37 patients with tumors located within 5 cm from the anal verge on colonoscopy, 27 (73%) underwent a sphincter-preserving procedure. No grade 3 and 4 proctitis or hematological toxicities were observed.

Conclusion

Preoperative chemoradiation therapy with capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation, with a low toxicity profile. This combined modality can be regarded as a safe and effective treatment for locally advanced rectal cancer.

Citations

Citations to this article as recorded by

MRI for Rectal Cancer: Staging, mrCRM, EMVI, Lymph Node Staging and Post-Treatment Response
David D.B. Bates, Maria El Homsi, Kevin J. Chang, Neeraj Lalwani, Natally Horvat, Shannon P. Sheedy
Clinical Colorectal Cancer.2022; 21(1): 10. CrossRef
MRI of Rectal Cancer: An Overview and Update on Recent Advances
Kartik S. Jhaveri, Hooman Hosseini-Nik
American Journal of Roentgenology.2015; 205(1): W42. CrossRef
Current Controversies in Neoadjuvant Chemoradiation of Rectal Cancer
P. Terry Phang, Xiaodong Wang
Surgical Oncology Clinics of North America.2014; 23(1): 79. CrossRef
Tailored rectal cancer treatment – a time for implementing contemporary prognostic factors?
A. Wibe, W. L. Law, V. Fazio, C. P. Delaney
Colorectal Disease.2013; 15(11): 1333. CrossRef
Oncologic Outcome After Preoperative Chemoradiotherapy in Patients With Pathologic T0 (ypT0) Rectal Cancer
Tae Young Jang, Chang Sik Yu, Yong Sik Yoon, Seok-Byung Lim, Seung-Mo Hong, Tae Won Kim, Jong Hoon Kim, Jin Cheon Kim
Diseases of the Colon & Rectum.2012; 55(10): 1024. CrossRef
Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
J G Kim, S K Sohn, D H Kim, J H Baek, S B Jeon, Y S Chae, K B Lee, J S Park, J H Sohn, J C Kim, I K Park
British Journal of Cancer.2005; 93(10): 1117. CrossRef
Preoperative Concurrent Chemoradiotherapy with Oral Fluoropyrimidine in Locally Advanced Rectal Cancer: How Good Is Good Enough?
Hyun Cheol Chung
Cancer Research and Treatment.2004; 36(6): 341. CrossRef

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Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5-Fluorouracil-Pretreated Patients with Metastatic Colorectal Cancer: Soo Mee Bang, Eun Kyung Cho, Jae Hwan Oh, Heung Moon Chang, Jin Seok Ahn, Jung Ae Lee, Young Iee Park, Myung Jue Ahn, Young Suk Park, Dong Bok Shin, Jae Hoon Lee; Cancer Res Treat. 2001;33(5):414-419. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.414

Abstract PDF

PURPOSE
To evaluate the efficacy and toxicity of oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer who previously treated with 5-FU-based chemotherapy.
MATERIALS AND METHODS
Between April 1999 and January 2001, thirty-two patients were enrolled in this study. Oxaliplatin 130 mg/m2 was given intravenously (IV) on day 1 as was 5-FU 500 mg/m2 IV followed by continuous infusion of 5-FU 3,000 mg/m2 and LV 100 mg/m2 for 48 hours administered every 3 weeks. Six patients had received 5-FU as an adjuvant setting and 26 patients as a palliative regimen.
RESULTS
The median age of the patients was 50 years (range; 19-69) and the dominant sites of metastasis were the liver, lung or both in 9, 5 and 2 patients respectively. In 30 evaluable patients, the overall response rate was 27% including 1 complete response and 7 partial responses. The median response duration was 28 weeks (95% confidence interval; 22~34 weeks) and the median progression free survival of all patients was 24 weeks (95% confidence interval; 15~33 weeks). A median 5 cycles (range; 2~9) and total 155 cycles were performed in 32 patients. 150 cycles were evaluable for toxicity. The most common hematologic toxicity was grade 1~2 anemia in 78 cycles (52%). Leukopenia (39%) and thrombocytopenia (23%) were fully reversible. The most common non-hematologic toxicity was nausea/vomiting (43/30%) followed by diarrhea (23%), hepatotoxicity (21%) and neurotoxicity (21%). One patient ceased therapy due to grade 4 diarrhea. No other severe toxicity interrupted this treatment.
CONCLUSION
Oxaliplatin, 5-FU and LV in combination showed significant activity in previously treated metastatic colorectal cancer with favorable toxicity.

Citations

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Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Research and Treatment.2005; 37(4): 212. CrossRef

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Efficacy of Combination Chemotherapy with Vinorelbine, Ifosfamide, and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer: Heung Moon Chang, Jung Ae Lee, Jin Seok Ahn, In Sook Woo, Young Iee Park, Jee Woong Son, Seung Joon Lee, Dong Kyu Kim, Eun Kyung Mo, Myung Jae Park, Myung Goo Lee, In Gyu Hyun, Ki Suck Jung, Young Suk Park; J Korean Cancer Assoc. 2000;32(3):612-618.

Abstract PDF: PURPOSE
To evaluate the efficacy and toxicity of combination chemotherapy with vinorelbine, ifosfamide, and cisplatin in patients with advanced non-small cell lung cancer.
MATERIALS AND METHODS
Patients with unresectable, pathologically proven non-small cell lung cancer who had no prior chemotherapy were eligible. Patients received vinorelbine (25 mg/m2, iv., D1 & 8), ifosfamide (1.5 g/m2, iv., D1-3 with mesna), and cisplatin (60 mg/m2, iv., D1). The treatment was repeated every 3 weeks.
RESULTS
Between degrees Ctober, 1997 and June, 1999, 26 patients were enrolled. Median age was 61. 1 patient had stage IIIA, 13 had stage IIIB, and 12 had stage IV. Patients with adendegrees Carcinoma were 15, squamous cell carcinoma were 11. Of 22 evaluable patients, objective responses were observed in 9 patients (response rate: 40.9%, CR: 1 (4.5%), PR 8 (36.4%)). Median duration of response was 48 weeks. Median overall survival was 52 weeks. Grade 3-4 leukopenia was observed in 10.2% of the 88 courses. There was 1 death related to febrile neutropenia. Non- hematologic toxicities were mild.
CONCLUSION
We concluded that combination chemotherapy with vinorelbine, ifosfamide, and cisplatin was effective and tolerable in patients with advanced non-small cell lung cancer, and phase III randomized trial is needed to compare this regimen to other cisplatin-based regimens.

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Phase II Multicenter Trial of Paclitaxel for Metastatic Breast Cancer: Jae Ho Byun, Sung Soo Yoon, Chan Hyung Park, Sung Rok Kim, Si Young Kim, Hyo Jin Kim, Soo Mee Bang, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 2000;32(3):545-552.

Abstract PDF: PURPOSE
To evaluate the efficacy and safety of paclitaxel for metastatic breast cancer patients who had received previous chemotherapy, we have performed phase II multicenter trial between December 1997 and December 1998.
MATERIALS AND METHOD
Thirty patients were accrued to this study and paclitaxel was administered at 175 mg/m2 as a 3-hour intravenous infusion every 3 weeks until the progression of the disease.
RESULTS
Objective response were observed in 13 of 30 patients (43.3%). There were 1 complete response (3.3%) and 12 partial responses (40%). Especially, 50% (11/22) of patients who had received prior anthracycline-containing regimens for adjuvant or metastatic disease responded to paclitaxel. Responses were observed in all sites of metastatic disease. One hundred forty-nine cycles of treatment were administered, with a median of six cycles per patient. Grade III and IV toxicities included neutropenia (24%), elevated liver enzyme (10%), peripheral neuropathy (10%), arthralgia/myalgia (23%), and alopecia (87%). No significant hypersensitivity type reaction or cardiac arrhythmia were seen. Median duration of response was 7.2 months.
CONCLUSIONS
These results suggested that paclitaxel is active therapeutic agent in metastatic breast cancer patients and it can be safely administered by 3-hour intravenous infusion with premedication.

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Antiemetic Effect of Granisetron plus Dexamethasone for the Patients Refractory to Metoclopramide , Dexamethasone and Lorazepam ( MDL ): Se Hoon Lee, Dong Wan Kim, Kyun Hae Jung, Soo Mee Bang, Jae Ho Byun, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):1027-1034.

Abstract PDF: PURPOSE
The combination of dexamethasone and granisetron provides effective prophylaxis in patients treated with high-dose cisplatin. We performed this study to evaluate the antiemetic effect of granisetron plus dexamethasone for the patients refractory to metoclo- pramide, dexamethasone, lorazepam (MDL) regimen.
MATERIALS AND METHODS
From 1996 to 1998, we administered the MDL regimen in patients who received high-dose cisplatin (more than 60 mg/m/day) for the first time. The granisetron plus dexamethasone were administered in the subsequent cycle for the patients refractory to the MDL regimen during the first or the second cycle of chemotherapy. Efficacies of treatment were assessed daily from days 1 to 5. Complete response was defined as the absence of vomiting episodes and major response as 1 or 2 episodes per day. Complete or major responses were considered effective.
RESULTS
Twenty patients received granisetron plus dexamethasone therapy. During the first 24 hours, complete and major responses were achieved in 75% and 15% respectively, thus it was effective in 90% of patients. For delayed vomiting (occurring during days 2 through 5), complete and major responses were achieved in 30% and 50% respectively, thus it was effective in 80%. Side effects included hiccups, headache, diarrhea, sedation, dizziness and insomnia, but discontinuation or dose adjustment was not needed.
CONCLUSION
The granisetron plus dexamethasone regimen was an effective antiemetic regimen for the patients refractory to the MDL regimen.

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IMVP-16/Pd (Ifosfamide/Methotrexate/VP-16/Prednisone) Combination Chemotherapy for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma: Ki Hyeong Lee, Young Iee Park, Heung Moon Chang, Tae You Kim, Keong Hae Jung, In Suk Woo, Young Hyuck Im, Dae Seog Heo, Yung Jue Bang, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(3):486-494.

Abstract PDF: PURPOSE
IMVP-16 (Ifosfamide/Methotrexate/VP-16) regimen consists of drugs that are not commonly used as the first-line therapy of non-Hodgkin's lymphoma. This study was performed to determine the efficacy of this relatively non-cross resistant regimen, with the addition of prednisone, in patients with primary refractory or relapsed non-Hodgkin's lymphoma.
MATERIALS AND METHODS
Patients with primary refractory or relpased intermediate to high grade non-Hodgkin's lymphoma were treated with ifosfamide (1000 mg/m2 iv, D1-5 with mesna), methotrexate (30 mg/m2 iv, D 3 & 10), VP-16 (100 mg/m2 iv, D 1-3), and prednisone (120 mg devided by 3 doses, D1-5). The treatment was repeated every 3 weeks.
RESULTS
Between Jan. 1988 and Aug. 1993, thirty eight patients were included. In 33 evaluable patients (4 loss-to follow up and 1 ineligibility) the median age was 49 years. The common histologic types were diffuse large cell type (52%) and immunoblastic type (18%). The proportion of patients with relapsed and refractory NHL was 39% and 61%, respectively. The rate of complete remission was 21% (7/33) and overall response rate was 48% (16/33). The median-response duration was 8 months (1.5~45+). Hematologic toxicities were tolerable. Non-hematologic side effects were also tolerable including stomatitis, peripheral neuropathy, and toxic hepatitis. Three treatment-related deaths were associated with sepsis, ARDS (adult respiratory distress syndrome) and acute gastrointestinal bleeding.
CONCLUSION
Based on these results, IMVP-16/Pd combination chemotherapy seems to have a moderate efficacy for the relapsed or refractory non-Hodgkin's lymphoma with tolerable toxicities.

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Clinicopathologic Comparison of Intermediate or High Grade Peripheral T-Cell Lymphoma with Diffuse B-Cell Lymphoma: Kyung Hae Jung, In Sook Woo, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Chul Woo Kim, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1997;29(1):136-145.

Abstract PDF: PURPOSE
Peripheral T-cell lymphoma (PTCL) derived from mature T cells forms morphologically diverse group of non-Hodgkin's lymphomas and the clinicopathologic features remain to be debated. In order to elucidate the specific characteristics of PTCL, comparison with a group of diffuse B-cell lymphomas (DBCL) was done.
MATERIALS AND METHODS
Between Dec. 1989 and Feb. 1993, clinical data of 67 cases of intermediate or high grade NHL identified as T-cell or B-cell origin by immunophenotyping was reviewed.
RESULTS
There were 30 cases of PTCL and 37 cases of DBCL. PTCL had more advanced stage and B symptoms at diagnosis. Frequent sites of extranodal involvement were bone marrow, nasal cavity/paranasal sinus, and skin in PTCL and gastrointestinal tract in DBCL. Based on NCI Working Formulation, 40% of PTCL and 14% of DBCL were high grade. Patients with DBCL had a better 3-year overall survival rate (67% vs 47%), however, there was no difference in complete remission rate and disease-free survival rate between two groups with intensive treatment. A subgroup of PTCL patients who had died earlier was found to have more advanced stage and poor performance status.
CONCLUSION
Although patients with PTCL had worse survival in advanced stage, the outcome of patients with PTCL who received intensive treatment was comparable to that of DBCL.

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Second - line , Chemotherapy with 5 - Fluorouracil Etoposide , Doxorubicin , Cisplatin , Cyclophosphamide , Adriamycin , Vincristine , Predais: Heung Moon Chang, Hyun Ah Kim, Won Seok Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1994;26(1):82-89.

Abstract PDF: There is no effective second-line chemotherapy for the advanced breast cancer. Previously CALGB reported that CAFVP combination chematherapy was more effective than the CMF or CMFVP combination chemotherapy for the advanced breast cancer. So we treated 38 advanced breast cancer patients with CAFVP combination chemotherapy, who had received previous chemotherapy, between June 1979 and September 1992. Median age was 41. 23 patients had prior mastectamy with adjuvant chemotherapy, 9 patients had prior mastectomy without adjuvant chemotherapy and 6 patients had initially stage IV lesions. All had been received prior chemotherapy. The menopausal status was as follows; 29 patients were premenopausal, 9 postmenopausaL The perfomance status was grade 0 to 1(ECOG) in 2l patients, 2 in 17. Treatment was cyclophosphamide 100 mg/m(2) po, day 1 l4, adriamycin 25 mg/m(2) iv, day 1 and 8, 5-fluorouracil 400 mg/m(2) iv, day 1 and 8, vincristine 1.4 mg/m iv, day 1 and 8, and pred- nisolone 60 mg/day po, day 1-14. The treatment was recycled every 4 weeks until the progression of the disease. Amang 26 patients with measurable lesions, 8(31%) achieved responses(l CR and 7 PR). Median duration of response was 7 months. Median survival for all patients was 20 months. Toxicity was as follows: leukopenia 35/, anemia 37%, thrombocytopenia 1%, N/V 21%. No treatment related death was observed during the treatment. It was concluded that CAFVP combination chemotherapy is not superior to other combination chemotherapy regimens, and myelosuppression is a major dose-limiting toxicity.

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A Case of Multiple Myeloma with Non - Hodgkin's Lymphoma: Heung Moon Chang, Won Seok Kim, In Shon, Chul Woo Kim, Dae Seog Heo, Yung Jue Bang, Seon Yang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1994;26(5):847-853.

Abstract PDF: Concurrent appearance of multiple myeloma with non-Hodgkins lymphoma was rare. We report a case of multiple myeloma with non-Hodgkin's lymphoma in a 75-year-old male. Multiple myeloma was diagnosed previously and then treated with combination chemotherapy. No evidence of the disease was seen after total 32 cycles of combination chemotherapy. Five years later, non-Hodgkins lymphama was developed in his left tonsil without recurrence of multiple myeloma. Whether both tumors derived from the same clone or not was unknown.

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The Postoperative Adjuvant Chemotherapy of Gastric Cancer with 5 - Fluorouracil , Adriamycin and Mitomycin - C ( FAM ): Young Suk Park, Heung Moon Chang, Keun Chil Park, Dae Seog Heo, Yung Jue Bang, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe, Soo Tae Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1994;26(6):853-860.

Abstract PDF: The postoperative adjuvant chemotherapy with FAM combination chemotherapy has been administered to 167 patients with stage IB, II, IIIA or IIIB gastric adenocarcinoma after cura- tive gastric resection between March l984 and December 1986. Chemotherapy was started within 4 weeks of surgery in most patiente. Treatment consisted of 5-FU 600 mg/m(2) (day 1, 8, 29 and 36), adriamycin 30 mg/m(2) (day l and 29), mitomycin-C 10 mg /m(2) (day 1) of an 8-week cycle. The cycle was repeated 3 times. Appropriate dose adjustment was made for hematologic and other toxicities. Twelve patients were ineligible for the study and excluded from the analysis. After median follow-up of 79 months, 65 of 155 treated patients recurred (41.9%). The sites of recurrent cancer were as follows: loco-regional, 35%, peritoneal, 23%, distant metastases, 23%, multiple sites, 19%. The 5-year disease-free survival rate was 57.1% and the 5-year overall survival rate was 60.6%. Treatment was well tolerated by the majority of patients and the common side effects were nausea and vomiting (51%). Sex, N stage and the number of involved lymph nodes affect- ed disease-free and overall survival. In conclusion, the postoperative adjuvant chemotherapy with FAM combination chemotherapy was safe and well tolerated. Although the results of FAM chemotherapy were more effec- tive than those of FM chemotherapy as historical control, we concluded that adjuvant chemo- therapy as given in this trial is not indicated as routine trestment in operable gastric cancer. So new trials of adjuvant chemotherapy for gastric cancer must be prospectively randomired and include a no-treatment control arm.

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Neoadjuvant Chemotherapy with High-dose Methotrexate , Adriamycin and Cisplatin for Non - Metastatic Osteosarcoma: Keun Seok Lee, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim, Sang Hoon Lee, Eui Keun Ham, Han Ku Lee; J Korean Cancer Assoc. 1996;28(6):1092-1104.

Abstract PDF: three non-metastatic osteosarcoma patients were treated with high-dose methotrexate, adriamycin, and cisplatin from October 1987 to May 1993. Median age was 18. The ratio of male to female was 16: 7. The patients received methotrexate 8g/§³ IV, day 1 and 8 with leucovorin rescue, adriamycin 25mg/§³ IV day 16~18, and cisplatin 75mg/§³ IV day 16, After two cycles of neoadjuvant chemotherapy, operation was done and then six cycles of adjuvant chemotherapy were given with the same regimen. One patient developed lung metastasis after two cycles of neoadjuvant chemotherapy, and the other patient died from sepsis associated with chemotherapy-induced neutropenia before operation. Therefore, 21 patients underwent operation. Among them, l9 patients underwent limb salvage operation. Of the five patients who relapsed, two patients had lung metastasis and another two patients had local recurrence, and one patient had both lung and brain metastasis. One year, three year, and five year disease-free survival rate were 84%, 68%, and 68%. One year, three year, and five year survival rate were 91%, 64%, and 53%, respectively. The site of the primary lesion was the only significant prognosis factor. Patients with the lesion of distal femur had poor prognosis.Histologic responses were assessed in 17 patients. Observed histologic responses were grade I necrosis in 35%, grade II necrosis in 65%. There was no grade III or IV necrosis. The disease-free survival rates and overall survival rates were not significantly different between grade I necrosis group and grade II necrosis group. Toxicities grade III or IV were as follows: leukopenia 32%, thrombocytopenia 9%, hepatotoxicity 14%, and infection 6% with one chemotherapy-related death. The pharmacokinetics of high-dose methotrexate with leucovorin rescue were studied in l0 patients. The highest concentration was achieved at the end of infusion(6 hour). The decay of the plasma concentration of methotrexate after completion of the infusion followed a two-compartment model with a T(1/2)￥a of 3.4¡¾1.9 hours and T(1/2)￥a of 8.0¡¾2.6 hours. The clearance was 55¡¾13ml/min/§³ and the volume of distribution was 8.2¡¾3.0 L/§³. In conclusion, neoadjuvant chemotherapy with high-dose methotrexate, adriamycin, and cisplatin is effective for treatment of the patients of osteosarcoma with preserving the limb function.

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