Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia: A literature review.

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/ refractory cancer. Here, we report a case of a 68‑year‑old gentleman having AML with high‑risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high‑dose (HD) cytosine arabinoside (Ara‑C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low‑intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)‑risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Can combination metronomic therapy overcome chemoresistance in cholangiocarcinoma: A literature review.

Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as radiation therapy, and complete resection is the main curative therapy for these patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is extremely poor. A 55‑year‑old woman presented at our hospital with abdominal pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not opt for standard chemotherapy and therefore received oral metronomic therapy with a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30 months. Presently, she is 57 months post diagnosis and 27 months post cessation of all treatment and continues to be in complete radiological remission. In the present report, we review the literature and discuss whether metronomic scheduling of biologic agents and anticancer drugs will be able to overcome chemoresistance and improve the outcome in cholangiocarcinoma. References for the review were identified through searches of Pubmed for the last 10 years as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Successful Response of Oral Etoposide for Refractory Neuroblastoma / 대한소아혈액종양학회지

Intensive chemotherapy with or without stem cell rescue has become widely accepted for treatment of neuroblastoma because increased dose-intensity correlates with improved response rates. For neuroblastoma that is resistant to intensive chemotherapy, further use of high-dose therapy is unlikely to be beneficial. For disease that recurs after myeloablative consolidation, high-dose salvage therapy may not be feasible because of poor bone marrow reserve and may not be justified in view of its morbidity in the absence of a realistic chance for cure. One treatment option in these difficult clinical settings is chronic oral administration of low-dose etoposide. However, there has been a few clinical reports for the experience of oral etoposide for refractory neuroblastoma. We now present 2 cases of successful response of oral etoposide for refractory neuroblastoma.

Oral Etoposide, Ifosfamide and Cisplatin in the Treatment of Extensive Disease Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The combination of cisplatin and etoposide has been a common first line regimen for the treatment of small cell lung cancer (SCLC). The schedule dependence, and equal efficacy, of the oral and intravenous dosing of etoposide has led to prolonged administration of oral etoposide, which is known to produce an encouraging response in SCLC. To improve the efficacy of the cisplatin/etoposide combination, we administered oral etoposide, with added ifosfamide, which had significant single agent activity against SCLC. We conducted this study to evaluate the efficacy and toxicity of the cisplatin, ifosfamide and oral etoposide (PIE) combination in patients with extensive small cell lung cancer. MATERIALS AND METHODS: Twenty-five patients with histologically confirmed extensive small cell lung cancer were enrolled into this study between January 2000 and May 2002. They were treated with, cisplatin at 20 mg/ m2/day, ifosfamide 1.5 g/m2/day, with mesna (all given intravenously on Days 1~3), and oral etoposide 50 mg/m2 on days 4~17. This cycle was repeated every 4 weeks for up to 6 cycles. We evaluated the corresponding disease responses and toxicities. RESULTS: The patients' characteristics were as follows: median age 65 years (32~75), 19 males and 6 females. The performance stati were ECOG 0 in 3 patients, ECOG 1 in 12 and ECOG 2 in 10. Sixteen patients had a partial response, 2 had a stable disease and 4 had a progressive disease. Thus, the overall objective response rate was 72.7% (95% CI: 49.6~88.4%), with a median response duration of 7 months (95% CI: 3.5~10.5 months). Myelosuppression was the major observed toxicity. Grades III and IV neutropenia were observed in 42 (46.1%) of the 91 cycles. Significant non-hematological toxicities (>or=Grade III) were uncommon, with the exception of nausea and vomiting. CONCLUSION: The response rate to the combination of cisplatin, ifosfamide and oral etoposide was similar to that of other combination chemotherapy studies in patients with extensive disease small cell lung cancer. The toxicity of the regimen was considered acceptable.

Concurrent Chemoradiation Therapy with Cisplatin and Oral Etoposide for Locally Advanced Non-small Cell Lung Cancer / 대한암학회지

PURPOSE: Prognosis of locally advanced inoperable non-small cell lung cancer (NSCLC) treated with radiation therapy alone has been disappointing. In recent years, concurrent chemoradiation therapy has potential of improving both local and metastatic disease-free survival. This phase II study was undertaken to determine the feasibility, toxicity, response rate, local control rate, and survival duration of locally advanced NSCL patients treated with concurrent chemoradiation using cisplatin and oral etoposide. MATERIAL AND METHODS: Forty-seven patients were enrolled and forty-one patients were evaluable. Chemotheray consisted of cisplatin 50 mg/m2/IV on days 1 and 8 and oral etoposide 100 mg/day on days 1 to 5 and 8 to 12 which was repeated, every 4 weeks for two cycles during radiation therapy. Radiation therapy was administered to a total dose of 6300 cGY. RESULTS: Among 41 evaluable patients, six patients achieved complete response, and twenty had partial response, for an overall response rate of 63.4% (95% confidence interval; 48.4% to 75.4%). Stable disease was reported in 10 patients (24.4%) and another 5 (12.2%) showed disease pro gression. Overall survival rate was 76% at 1 year, 34% at 2 years. Median survival duration was 17 months (range; 3 to 41 ). Eighty-three percents of patients had radiation pneumonitis but only one patients needed medical treatment. CONCLUSION: Concurrent chemoradiation therapy with cisplatin and oral etoposide at this level is a well tolerated and feasible.

Prolonged Oral Etoposide in Combination with Intravenous Cisplatin for Advanced Non-small Cell Lung Cancer / 대한암학회지

PURPOSE: Etoposide is a schedule-dependent agent and has a synergistic activity with cisplatin. We evaluated the response rate and the toxicity of prolonged oral etoposide in combination with intravenous cisplatin for the previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between April 1996 and February 1998, 71 patients were enrolled. The median age was 61 years (range, 36~75) and male: female ratio was 54: 17. Fourteen patients had stage IIIB disease and 57 had stage IV. Sixty-two patients had ECOG performance status of 0 or 1, and 9 had 2. Forty-eight patients had adenocarcinoma, 19 had squamous cell carcinoma and 4 had poorly differentiated NSCLC. Treatment consists of daily oral etoposide 50 mg/m in 2 divided doses for 21 days and intravenous cisplatin 60 mg/m on day 1. The treatment was repeated every 28 days. RESULTS: Sixty-four of 71 patients were evaluable. Complete response and partial response were observed in 1 and 21 patients, respectively. The overall response rate was 34.4% (95% confidence interval 23.9~46.6%) and the median response duration was 30 weeks (range 13-53 weeks). The median survival of 71 patients was 56 weeks (range 3. 96+ weeks). There was a significantly longer survival in responders (p=0.035). Toxicities were evaluated by WHO criteria. Hematologic toxicities of grade 3, 4 were as follows: anemia 12.3%, leukopenia 8.7%, neutropenia 19.2%, thrombocytopenia 1.8%. Non-hematologic toxicities of grade 3, 4 were as follows: nausea and vomiting 5.9%, stomatitis 14.7%, diarrhea 1.5%. Early treatment-related death occurred in 2 patients (2.8%) due to sepsis. CONCLUSION: Combination chemotherapy with prolonged oral etoposide and intravenous cisplatin is easy to administer and has moderate activity with acceptable toxicities for NSCLC.

Clinical Efficacy of Combination Chemotherapy with Cisplatin , Ifosfamide , and Oral Etoposide ( PIE ) in Advanced Non - Small Cell Lung Cancer / 대한암학회지

PURPOSE: A prolonged administration of etoposide increases its effectiveness on the suggestion that pralonged maintenance of low levels is an important factor in determining its activity. Many studies have been tried to define the efficacy of combination of oral etoposide with other chemotherapeutic drugs such as cisplatin, 5-FU, and ifosfamide in patients with advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the effectiveness and toxicities of combination chemotherapy of oral etoposide with intravenous cisplatin and ifosfamide in advanced NSCLC patients. MATERIALS AND METHODS: Thirty-three patients with inoperable NSCLC who had measurable diseases and had not been treated with chemotherapeutic drug, were enrolled in this study (from May 1995 to April 1998). Treatment consisted of intravenous cisplatin (20 mg/m(2)/day, Day 1-3) and ifosfamide (1,800 mg/m(2)/day, Days 1-3) with Mesna (1,100 mg/m(2)/day, Days 1-3), and oral etoposide (50 mg/m(2)/day, Days 4-17). This treatment was repeated every 4 weeks. Patients showing stable disease or a better response were continued on treatment with the range of one to nine cycles (medium: 3 cycles). All patients were evaluated for the response, survival, and toxicity of this combination chemotherapy. RESULTS: Eleven patients showed either complete responses [CR, 3 (9%)] or partial responses [PR, 8 (24%)]. The median number of treatment cycles were 5 (range, 3-9) for responders and 2 (range, 1-7) for non-responders. The responders had median response duration of 10 months and the overall survival of 12 months. The overall survival of responders were longer than that of non-responders (median 19 vs 5 months, p 0.0232). The toxicities of this treatment were tolerable without treatment related death. Limiting toxicities were myelosuppression and oral mucbsities, Grade 3 or 4 leukopenia and oral mucosities were observed in 34% and 9%, respectively. CONCLUSION: The combination of cisplatin, ifosfamide, and oral etoposide produced encouraging response rates and median survival duration in patients with response. Further study of this combination is warranted in comparison with standard cisplatin+etoposide regimen or intravenous etoposide, cisplatin and ifosfamide regimen.