BACKGROUND: Patients with transformed chronic myelogenous leukemia(CML) and advanced myelodysplastic syndrome(MDS) have poor prognosis. The aim of this study is to evaluate the feasibility of second chronic phase induction in accelerated phase(CML-AP) or blastic crisis of CML(CML-BC) and remission induction in advanced MDS by combining topoisomerase I inhibitor (topotecan) with topoisomerase II inhibitor(mitoxantrone). METHODS: Twenty-four evaluable patients were entered on this study with a median age of 34 years. Eighteen patients with transformed CML(7 CML-AP, 11 CML-BC) and 6 patients with advanced MDS were treated. Topotecan was administered as 1.5 mg/m2/day by continuous infusion over 24 hours daily for 5 days every 4 to 8 weeks until remission. To enhance the tumoricidal effects, mitoxantrone(12 mg/m2/day, Days 1-3) was added. RESULTS: Eight patients(33+ACU-) achieved a complete remission(CR). Four of 7 patients with CML-AP(57+ACU-), 2 of 4 patients with CML-lymphoid blastic crisis (-LBC)(50+ACU-) and 2 of 6 patients with advanced MDS(33+ACU-) had CR lasting more than 45 days(45 to 400 days). There was no CR in the patients with CML-myeloid blastic crisis(-MBC). The dose level of 1.5 mg/m2/day(7.5 mg/m2/course) of topotecan was well tolerated in all patients. Mucositis occurred in 69+ACU- of patients (severe in 5+ACU-) and diarrhea in 67+ACU-(severe in 8+ACU-). In addition, there were no new or unexpected toxicities in the patients who were treated at this dose(7.5 mg/m2/course). In patients who recovered their neutrophil count, the absolute neutrophil count(ANC) remained below 500/microL for a period of 13 to 58 days(median 21 days) and the time to ANC recovery was associated with pretreatment severity of bone marrow fibrosis(mainly CML patients). Likewise, in the patients who recovered unsupported platelets, the platelets remained below 20,000/microL for a period of 0 to 37 days (median 19 days). CONCLUSION: The combination of topotecan-mitoxantrone has shown modest activity in CML-AP, CML-LBC and advanced MDS with acceptable toxicities.
Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use+ACo- ; Antineoplastic Agents, Combined/adverse effects ; Female ; Human ; Leukemia, Myeloid, Chronic/drug therapy+ACo- ; Male ; Middle Age ; Myelodysplastic Syndromes/drug therapy+ACo- ; Topotecan/administration +ACY- dosage+ACo-

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage

The aim of this study was to evaluate the survival of 395 previously untreated cervical cancer patients with at least one high risk factor following concurrent chemoradiation and to assess the toxicities. Two different chemotherapy regimens were used for concurrent chemoradiation. In the patients with squamous cell carcinoma, 100 mg/m2 of cisplatin was infused intravenously, followed immediately by five consecutive daily administrations of 5-fluorouracil, 1,000 mg/m2/day, each infused intravenously over 24 hr. As for the patients with adenocarcinoma, 70 mg/m2 of cisplatin, 250 mg/m2 of cytoxan and 45 mg/m2 of adriamycin were administered intravenously on days 1, 2, and 3, respectively. The 5-year survival rate was 54.4+ACU- with stage III and IV, 62.6+ACU- with lymph node metastasis on computed tomogram or MRI, 77.9+ACU- with stage I-II disease with lesion size +AD4- or +AD0-4 cm, and 50.3+ACU- with small cell carcinoma or adenocarcinoma. Side effects from concurrent chemoradiation such as nausea, vomiting, and alopecia were present in all 395 cases. Anemia, leukopenia, thrombocytopenia, hepatotoxicity, and nephrotoxicity were observed to varying degrees, but there was no toxic death. This study suggests that cisplatin-based concurrent chemoradiation in treating cervical cancer patients with high risk factors is effective and relatively well tolerated, with acceptable toxicity.
Adenocarcinoma/radiotherapy ; Adenocarcinoma/mortality ; Adenocarcinoma/drug therapy ; Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use+ACo- ; Antineoplastic Agents, Combined/adverse effects ; Carboplatin/administration +ACY- dosage ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/drug therapy ; Cervix Neoplasms/radiotherapy+ACo- ; Cervix Neoplasms/mortality ; Cervix Neoplasms/drug therapy ; Chemotherapy, Adjuvant/adverse effects ; Cisplatin/administration +ACY- dosage ; Combined Modality Therapy ; Comparative Study ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/administration +ACY- dosage ; Female ; Fluorouracil/administration +ACY- dosage ; Gastrointestinal Diseases/etiology ; Gastrointestinal Diseases/epidemiology ; Hematologic Diseases/etiology ; Hematologic Diseases/epidemiology ; Hepatitis, Toxic/etiology ; Hepatitis, Toxic/epidemiology ; Human ; Kidney Diseases/epidemiology ; Kidney Diseases/chemically induced ; Korea/epidemiology ; Life Tables ; Lymphatic Metastasis ; Middle Age ; Particle Accelerators ; Radiotherapy, High-Energy+ACo-/adverse effects ; Retrospective Studies ; Risk ; Survival Analysis ; Treatment Outcome

The aim of this study was to evaluate the survival of 395 previously untreated cervical cancer patients with at least one high risk factor following concurrent chemoradiation and to assess the toxicities. Two different chemotherapy regimens were used for concurrent chemoradiation. In the patients with squamous cell carcinoma, 100 mg/m2 of cisplatin was infused intravenously, followed immediately by five consecutive daily administrations of 5-fluorouracil, 1,000 mg/m2/day, each infused intravenously over 24 hr. As for the patients with adenocarcinoma, 70 mg/m2 of cisplatin, 250 mg/m2 of cytoxan and 45 mg/m2 of adriamycin were administered intravenously on days 1, 2, and 3, respectively. The 5-year survival rate was 54.4+ACU- with stage III and IV, 62.6+ACU- with lymph node metastasis on computed tomogram or MRI, 77.9+ACU- with stage I-II disease with lesion size +AD4- or +AD0-4 cm, and 50.3+ACU- with small cell carcinoma or adenocarcinoma. Side effects from concurrent chemoradiation such as nausea, vomiting, and alopecia were present in all 395 cases. Anemia, leukopenia, thrombocytopenia, hepatotoxicity, and nephrotoxicity were observed to varying degrees, but there was no toxic death. This study suggests that cisplatin-based concurrent chemoradiation in treating cervical cancer patients with high risk factors is effective and relatively well tolerated, with acceptable toxicity.
Adenocarcinoma/radiotherapy ; Adenocarcinoma/mortality ; Adenocarcinoma/drug therapy ; Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use+ACo- ; Antineoplastic Agents, Combined/adverse effects ; Carboplatin/administration +ACY- dosage ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/drug therapy ; Cervix Neoplasms/radiotherapy+ACo- ; Cervix Neoplasms/mortality ; Cervix Neoplasms/drug therapy ; Chemotherapy, Adjuvant/adverse effects ; Cisplatin/administration +ACY- dosage ; Combined Modality Therapy ; Comparative Study ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/administration +ACY- dosage ; Female ; Fluorouracil/administration +ACY- dosage ; Gastrointestinal Diseases/etiology ; Gastrointestinal Diseases/epidemiology ; Hematologic Diseases/etiology ; Hematologic Diseases/epidemiology ; Hepatitis, Toxic/etiology ; Hepatitis, Toxic/epidemiology ; Human ; Kidney Diseases/epidemiology ; Kidney Diseases/chemically induced ; Korea/epidemiology ; Life Tables ; Lymphatic Metastasis ; Middle Age ; Particle Accelerators ; Radiotherapy, High-Energy+ACo-/adverse effects ; Retrospective Studies ; Risk ; Survival Analysis ; Treatment Outcome