Third‑line chemotherapy after resistance to Etoposide, Cisplatin‑ Etoposide, Methotrexate, Actinomycin (EP‑EMA) in high risk gestational trophoblastic neoplasia: Experience at the Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#To describe the experience of the Division of Trophoblastic Diseases of the Philippine General Hospital with the various third‑line chemotherapeutic regimens among high‑risk gestational trophoblastic neoplasia (GTN) patients who experienced resistance after receiving the etoposide, cisplatin–etoposide, methotrexate, actinomycin (EP‑EMA) regimen@*Materials and Methods@#This was a 17‑year descriptive study that included all patients who used various salvage chemotherapy after resistance to EP‑EMA as treatment for metastatic, high‑risk GTN at the Philippine General Hospital from January 2002 to December 2018. The medical records of eligible patients were retrieved and assessed. All abstracted data were analyzed retrospectively. Descriptive statistics were used to compute for percentages for the various demographic characteristics of the sample population@*Results@#From January 2002 to December 2018, a total of 291 patients with metastatic, high‑risk gestational GTN were treated at the Philippine General Hospital. Of these, only seven patients received various third‑line chemotherapy regimens after resistance to EP‑EMA. One patient was excluded due to incomplete data. Among the third‑line chemotherapeutic regimens used, 3 patients received paclitaxel/carboplatin, two of whom went into remission while one expired. One patient had vincristine, bleomycin, and cisplatin (VBP) with two adjunctive surgeries in the form of hysterectomy and thoracotomy. She also went into remission. Two patients received paclitaxel–cisplatin/paclitaxeletoposide (TP/TE) as third line of treatment. The first was shifted back to EP‑EMA and eventually developed chemoresistance to EP‑EMA and had multiple toxicities. After multidisciplinary conference with the patient and family, they decided to go home and refused further chemotherapy. The other patient had TP/TE followed by bleomycin–etoposide–cisplatin, with adjunctive hysterectomy. Despite multiple cycles of chemotherapy, the disease persisted. She was offered palliative care and the family decided to bring her home. Both patients eventually expired at home@*Conclusion@#No conclusion can be made about the most effective third line chemotherapy for resistant high‑risk GTN because of the limited cases included in this study. An individualized approach is still recommended. Physicians and centers for patients caring for such patients are encouraged to report their experience to improve the management of future patients

Factors affecting remission to salvage chemotherapy with EtoposideCisplatin/Etoposide-MethotrexateActinomycin D (EP-EMA regimen) among chemoresistant high-risk Gestational Trophoblastic Neoplasia patients admitted in a tertiary institution: A 10-year retrospective descriptive study / Philippine Journal of Obstetrics and Gynecology

Background@#Approximately 20%–25% of high-risk gestational trophoblastic neoplasia (GTN) patients initially treated with first-line chemotherapy regimen develop resistance to the regimen. The EP-EMA (Etoposide-cisplatin and etoposide, methotrexate and actinomycin D) regimen is the most commonly utilized second-line agent. @*Objective@#This study aimed to identify factors leading to remission using etoposide and cisplatin-etoposide, methotrexate, and Actinomycin D (EP-EMA) as salvage chemotherapy among resistant high-risk GTN.@*Methods@#This is a retrospective descriptive study that reviewed the medical records of patients admitted in the section of trophoblastic diseases diagnosed with high-risk GTN from January 2006 to December 2015. @*Results@#The medical records of 20 patients were retrieved and reviewed. The complete remission rate with EP-EMA is 60% (12/20). The overall survival rate for 1 year is 70% (14/20). Only 20% of the patients went home against advice and did not complete treatment. This regimen reported toxicities ranging from Grade 2–4 myelosuppression and electrolyte imbalance. Forty-five percent had Grade 4 neutropenia and Grade 2 anemia and 20% had Grade 2 thrombocytopenia. Hypokalemia and hypomagnesemia were noted in 8 patients (40%). Although not statistically significant, a trend showed that those in the remission group mostly had Stage III diseases with metastasis only in the lungs, prognostic score of between 7 and 12, and with beta-human chorionic gonadotropin (β-hCG) levels <10,000 mIu/ml at the start of EP-EMA treatment.@*Conclusion@#There is an improved response with EP-EMA chemotherapy across the years in our institution. Factors such as stage of disease, pulmonary metastasis, and low β-hCG at the start EP-EMA chemotherapy denote a possible good response and may contribute to patients' complete remission with EP-EMA chemotherapy. However, further studies with larger patient sample size are recommended to support the latter.

Salvage therapy for postoperative recurrence or metastasis in stage T3 N0 M0 thoracic esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective To analyze the efficacy of salvage therapy for postoperative recurrence or metastasis in patients with stage T3 N0 M0 thoracic esophageal squamous cell carcinoma ( ESCC ) and its influencing factors. Methods A retrospective analysis was performed in 108 patients with postoperative recurrence or metastasis in stage T3 N0 M0 thoracic ESCC who were admitted to our hospital from 2008 to 2009. In those patients, 59 had locoregional recurrence ( LR) , 26 distant metastasis ( DM) , and 23 both LR and DM. After recurrence, 53 patients received supportive therapy, 32 salvage radiotherapy, 9 chemotherapy, and 14 chemoradiotherapy. The overall survival ( OS) rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. The univariate and multivariate prognostic analyses were performed using the log?rank test and the Cox regression model, respectively. Results The follow?up rate was 100%. In all patients, the 1?, 3?, and 4?year OS rates were 29?9%, 16?5%, and 14?4%, respectively;the median OS time was 6 months. The univariate analysis showed that recurrence pattern and salvage therapy were associated with OS after recurrence ( P=0?017;P=0?000) . The multivariate analysis showed that salvage therapy was the only independent factor for OS after recurrence ( P=0?000) . Compared with supportive therapy, the risk of death after chemotherapy, radiotherapy, or chemoradiotherapy was reduced by 76?7%, 76?7%, and 86?1%, respectively. Conclusions The treatment outcomes are poor in patients with postoperative recurrence of stage T3 N0 M0 thoracic ESCC. Salvage therapy can substantially improve OS after recurrence.

Problems in hematopoietic stem cell transplantation for treating re-lapsed or refractory Hodgkin lymphoma / 中国肿瘤临床

The standard therapy for relapsed/refractory Hodgkin lymphoma (RR-HL) consists of salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). Salvage therapy is not obviously superior to commonly used regimens such as BEAM, CBV, and IGEV. Functional imaging with 18F-fluoro-2-deoxy-D-glucose positron emission tomogra-phy scanning is a critical predictor of the outcome after the completion of salvage chemotherapy and before ASCT. Meanwhile, re-duced-intensity conditioning allogeneic stem cell transplantation may induce a strong response in some patients with relapsing or pro-gressing HL after ASCT. In this study, we reviewed some problems in hematopoietic stem cell transplantation for treating RR-HL.

Chemotherapy for metastatic colorectal cancer after failure of treatment with irinotecan and oxaliplatin / 中国肿瘤临床

Objective:This retrospective study aims to determine the efficacy of chemotherapy and improve a salvage chemother-apy agent for metastatic colorectal cancer (MCRC) after failure of treatment with irinotecan and oxaliplatin. Methods:Between Janu-ary 2002 and March 2013, 37 patients with metastatic MCRC who had progressed after treatment with irinotecan and oxaliplatin were analyzed for their response rate (RR) and progression-free survival (PFS). Results:The overall RR of the 37 patients was 13.51%, with 5 cases of partial response (PR), 12 cases of disease stabilization (SD), and 20 cases of progression (PD). Compared with other chemo-therapy regimens, treatment with a pemetrexed-based chemotherapy agent had a higher RR (17.64%vs. 10.00%, P=0.64) without a lon-ger PFS (2.00 months vs. 1.63 months, HR=0.79, 95%, CI:0.35 to 1.78, P=0.58). Compared with other chemotherapy regimens, treat-ment with a raltirexed-based chemotherapy agent had a higher RR (16.67%vs. 12.00%, P=0.34) without a longer PFS (1.58 months vs. 1.90 months, HR=2.24, 95%, CI:0.98 to 5.12, P=0.06).Conclusion:In patients with MCRC after failure of treatment with irinotecan and oxaliplatin, a pemetrexed-based or raltirexed-based chemotherapy agent may beneficial during salvage treatment and is therefore worthy of further study.

Rituximab and ESHAP as Second-line Therapy for Relapsed or Primary Refractory Diffuse Large B Cell Lymphoma: The Experience of a Single Center in Korea

BACKGROUND: The remission status prior to autologous stem cell transplantation (ASCT) influences the transplantation outcome in patients with relapsed or primary refractory diffuse large B cell lymphoma (DLBCL), a complete response (CR) generally being more favorable than a partial response (PR). This study investigated whether the addition of rituximab to the ESHAP chemotherapy regimen (R-ESHAP) could improve the CR rate in patients with relapsed or primary refractory DLBCL. METHODS: Retrospective analysis was performed with DLBCL registry data. RESULTS: Sixteen patients who had previously received one course of chemotherapy were administered R-ESHAP (median 3 cycles; range 1~6). The overall response rate of 75% (CR=50%; PR=25%), was significantly better than that achieved with ESHAP alone in 13 historical controls (31%; P=0.027). The toxicity was tolerable, with two febrile neutropenia episodes in 51 treatment cycles. Seven of the 12 responders to R-ESHAP underwent ASCT with BEAM. After a median follow-up of 17 months, the median survival endpoints have not been reached. CONCLUSION: R-ESHAP appears to induce high CR rates in relapsed or refractory DLBCL with acceptable toxicity.

Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients. MATERIALS AND METHODS: Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on the first day plus LV 20 mg/m2 over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m2 followed by a 22-hour continuous infusion of 600 mg/m2 on days 1~2. The treatment was repeated at 2 week intervals. RESULTS: The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths. CONCLUSIONS: The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.

FLLP combination chemotherapy in 5-Fluorouracil refractory colorectal cancer patients / 대한내과학회지

BACKGROUND: There are few therapeutic options in patients with colorectal cancer that progressed or recurred after initial 5-fluorouracil (5-FU) therapy. Many different 5-FU-based regimens and biochemical modulations that can potentiate the cytotoxic effects of 5-FU have been investigated in these patients. We evaluated the efficacy and toxicity of combination of 5-FU, leucovorin, levamisole and cisplatin(FLLP) salvage combination chemotherapy in progressive or recurrent colorectal cancer after 5-FU/leucovorin chemotherapy. METHODS: Twenty-eight patients were enrolled in this study from April 1995 to July 1999. Patients received cisplatin (60 mg/m2) administerd on day 1, followed by leucovorin (20 mg/m2) and 5-FU (375 mg/m2) by rapid intravenous push for 5 consecutive days on day 1~5. Levamisole was given orally at a dose 50 mg three times a day on day 1~3 & day 15~17. Treatment courses were repeated in 4-week intervals. RESULTS: Twenty-two patients were evaluable after treatment. Objective tumor response was in 4 of 22 (18.2%). The complete response, partial response, stable disease were 4.5% (1/22), 13.7% (3/22), 31.8% (7/22) respectively. The median response duration was 5.5 months. The median time to progression was 5.8 months. The overall median survival duration was 8.7 months and response group lived significantly longer than non-response group (not yet reached vs. 7.9 month, p=0.03). WHO grade 3-4 leukopenia occurred in 14%, nausea and vomiting 9%, but there was no treatment related death. CONCLUSION: We concluded that evaluation of this regimen appears relatively safe, with modest response as a salvage chemotherapy in patients who were previously exposed to 5-FU containing regimen.

The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma / 대한암학회지

PURPOSE: Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy. MATERIALS AND METHODS: Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. RESULTS: Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care. CONCLUSION: Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

Protracted Venous Infusion of 5-Fluorouracil as a Chemotherapy in Colorectal Cancer / 대한암학회지

PURPOSE: The administration of 5-fluorouracil (5-FU) by protracted intravenous infusion is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancers. This study was performed to evaluate the response rate and toxicities of protracted infusion of 5-FU in patients with advanced or recurrent colorectal cancers who had been treated with 5-FU by bolus or shortterm continuous administration. MATERIALS AND METHODS: Between March 1995 and June 1997, twenty-eight patients with advanced colorectal cancer previously exposed to 5-FU based chemotherapy were enrolled in this triaL Patients received 5-FU (250 mg/m(2)/day days 1-28) or 5-FU plus leucovorin (5-FU; 200 mg/m/day days 1-28, leucovorin; 20 mg/m IV days 1, 8, 15, 21) by ambulatory infusion pump. Treatment course was repeated every 42 days until disease progression. RESULT: Twenty-eight patients entered. All 28 patients were assessable for response and toxicity. Five (19%) patients achieved a partial response, with the median response duration of 15 weeks (range; 7-22 weeks), and median survival time of entire patients was 54 weeks (range 7-151+ weeks). Gastrointestinal toxicity, specifically stomatitis was a major toxicity (grade 2, 12%; grade 3, 4%), but hand-foot syndrome was less frequent (5%) compared with other trials with protracted infusion of 5-FU reported in the literature. Hematologic toxicity was generally of low grade. CONCLUSION: Prolonged intravenous infusion of 5-FU can produce a response rate of 19% with low toxicity among patients refractory to bolus or short-term infusion of S-FU.