EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma.

1993 ◽  
Vol 11 (8) ◽  
pp. 1573-1582 ◽  
Author(s):  
W H Wilson ◽  
G Bryant ◽  
S Bates ◽  
A Fojo ◽  
R E Wittes ◽  
...  

PURPOSE Based on in vitro evidence that tumor cells are less resistant to prolonged exposure to low concentrations of the natural product class, compared with brief higher concentration exposure, we developed a chemotherapy regimen (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone [EPOCH]) in which the natural products are administered as a continuous infusion. PATIENTS AND METHODS This is a phase II study of etoposide, vincristine, and doxorubicin, administered as a 96-hour continuous infusion, with intravenous (IV) bolus cyclophosphamide and oral prednisone (EPOCH) in 74 consecutive patients who relapsed from or failed to respond to most of the same drugs administered on a bolus schedule. Patients with aggressive lymphomas who achieved a good response after EPOCH were eligible to undergo bone marrow transplantation. RESULTS Patients with intermediate- or high-grade lymphoma comprised 76% of this series and 77% had stage IV disease. Seventy-one percent had previously received all of the drugs contained in the EPOCH regimen and 92% had received at least four of the drugs. Seventy patients were assessable for response, of whom 19 (27%) achieved a complete remission (CR) and 42 (60%) a partial remission (PR). Among 21 patients who had no response to prior chemotherapy, 15 (71%) responded, but only one achieved a CR. Patients who relapsed from an initial CR had a 100% response rate, with 76% CRs. With a median potential follow-up duration of 19 months, there was a 28% probability of being event-free at 1 year. Toxicity was primarily hematologic with neutropenia during 51% of cycles, but only a 17% incidence of febrile neutropenia. Gastrointestinal, neurologic, and cardiac toxicity were minimal. CONCLUSION EPOCH chemotherapy was well tolerated and highly effective in patients who were resistant to or relapsed from the same drugs administered on a bolus schedule, suggesting that continuous infusion of the natural drug component of this regimen is capable of partially reversing drug resistance and reducing toxicity. Dose-intensity (DI) was > or = that achieved in primary treatment regimens for aggressive lymphomas.

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16526-e16526
Author(s):  
Selim Yalcin ◽  
Omer Dizdar ◽  
Nadire Kucukoztas ◽  
Samed Rahatli ◽  
Ozlem Ozen ◽  
...  

e16526 Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5518-5518
Author(s):  
D. M. O'Malley ◽  
C. Nagel ◽  
L. A. Cantrell ◽  
L. Havrilesky ◽  
M. Liotta ◽  
...  

5518 Background: There is currently no consensus regarding the management of advanced stage uterine MMT. In an effort to better define postoperative treatment modalities and their associated outcomes, we retrospectively reviewed factors that influence progression and survival. Methods: A retrospective, multi-institution study of women diagnosed from 1997–2007 was performed. Post-operative treatment included either observation (OBS), RT (brachytherapy, whole pelvic, or combination), chemotherapy (CT) alone or with RT (CT+RT). The majority of chemotherapy regimens included carboplatinum/paclitaxel, Ifosfamide/cisplatin, cisplatin/adriamycin, Data collected included time to recurrence, overall survival and sites of recurrence. Statistics included t-test, ANOVA and Kaplan Meier. Results: 119 patients were identified with late stage uterine MMT. 81 had stage III disease and 38 had stage IV disease. The median age at diagnosis was 67 years (range: 30–86). 70 (59%) were Caucasian and 48 (40%) were African-American. 116 (87%) were optimally debulked and their survival further analyzed. 18 (15%) were observed and 9 of these patients recurred. This group had the poorest median progression free survival (PFS) of 3.4 months. The majority (N = 50, 49%) of late stage patients underwent adjuvant CT with a median PFS of 13.3 months and median OS of 15.6 months. Of these patients 33 (66%) recurred. 18 (17 %) patients underwent RT alone with a median PFS of 12.4 months and OS of 14.9 months. 14 (78%) of these patients recurred. 20 patients (19%) underwent a combination of CT and RT and 11 (55%) experienced recurrences . The combination therapy group had the longest median PFS of 14.3 months and OS of 17.2 months (p = 0.27). Conclusions: Chemotherapy had become the standard therapy for advanced stage MMT however the addition of radiation has not been established. Patients diagnosed with advanced stage MMT can achieve long-term DFS in a minority of patients (33%) treated with chemotherapy. We showed that the addition of radiation to adjuvant chemotherapy showed a slight improvement over chemotherapy alone yet the optimal therapy has yet to be defined. This retrospective review highlights the need for prospective trials of new therapeutic agents and treatment regimens for women with advanced stage uterine MMT. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20587-e20587
Author(s):  
Nabil Habib ◽  
Hamid Elia Daaboul ◽  
George Hage ◽  
Abdo Jabbour ◽  
Hind Zeitouni ◽  
...  

e20587 Background: Hydroxysterols are oxygenated derivatives of cholesterol. They have been shown to interfere with proliferation and cause the death of many cancer cell types, such as leukaemia, glioblastoma, colon, breast and prostate cancer cells. They control the transcription and the turnover of the key enzyme in cholesterol synthesis. Hydroxysterols interfere with PI3K/AKT, MAPK/ERK, hedgehog and Wnt pathways of proliferation and differentiation. When administered in vitro to cancer cell lines, hydroxysterols invariably both slow down proliferation and provoke cell death. Many of these compounds show antitumor activity in experimental models and most of them are very toxic. (24-ethyl-cholestane- 3β,5α,6α-triol) is the first oxysterol being tested in the clinic. It is also one of the safest in this class of compounds. Methods: We have treated with this new drug 18 patients suffering from Non-small cell lung cancer (NSCLC); sixteen males and two females. Thirteen had adenocarcinomas and five had squamous-cell carcinoma. The median age was 65. Sixteen patients had a stage IV disease and two had a stage III disease. Seven had a PS: 1, seven had a PS: 2 and four had a PS:3. Seventy-five percent were symptomatic and fifty percent were taking pain killers. Six patients only did not receive previous chemotherapy and five received radiotherapy. Patients received daily 10 mg/Kg of oral (24-ethyl-cholestane- 3β,5α,6α-triol) divided in 3 equal doses, until disease progression. Results: Twelve patients had a partial response (PR), three patients had a stable disease (NC) and three patients had a disease progression (PD). The median duration of response was 8 months but 2 patients are still under treatment. No toxicity was observed so ever. Seventy-five percent of symptomatic patients had a remarkable symptom control. Conclusions: These encouraging results make this new and safe drug a good candidate for further clinical trials either alone or in association with other drugs for the treatment of NSCLC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7107-7107
Author(s):  
Yaman Suleiman ◽  
Milan Radovich ◽  
Luis Rojas ◽  
Ryan Frederick Porter ◽  
Madison Conces ◽  
...  

7107 Background: Thymoma and thymic carcinoma (TC) are rare tumors, but represent the most common neoplasms of the anterior mediastinum. The vast majority of TET present in early stages with little data existing on factors influencing survival in patients with advanced or stage IV disease. Methods: A retrospective analysis was performed on patients with confirmed TET (histology and with tissue blocks) seen at IUSCC diagnosed between 1976 and 2011. Patient demographics including Masaoka stage, histology, and sites of metastasis were linked with progression free survival (PFS) and overall survival (OS). Results: Our analysis included 102 patients with stage IV TET: 50 presented de novo and 52 developed stage IV disease following primary treatment. When stratified by tumor histology (thymoma or TC), patients with TC had considerably poorer PFS (p=1.87x10-7) and OS (p=7.72x10-8). The median PFS for TC was 13 months (range 4 to 39) and the MST was 36 months (range 4 to 115). PFS at 5-years was 21% and 0% but the five-year OS was 84% and 29% for thymoma and TC, respectively. Ten year OS was 55% for patients with thymoma and 0% for those with TC. Pleural (>3 vs. <3) metastases were significantly associated with a better PFS (p=0.036) and OS (p=0.0003). The PFS and OS of patients with lung nodules trended with those with pleural metastasis. Patients with pleural metastasis and lung nodules sites did considerably better than those with visceral disease (PFS, p=0.004, OS, p=2.09x10-5). Conclusions: Patients with TC have significantly poorer PFS and OS when compared to thymoma confirming that TC is a distinct clinical entity from thymoma. Patients with thymoma may have prolonged survival, despite having residual disease. Although current staging places patients with pleural metastasis (Masaoka stage IVA) and those with lung nodules (stage IVB) as separate categories, our data would suggest that those with lung nodules have similar survival with those who have pleural metastasis.


2002 ◽  
pp. 171-182 ◽  
Author(s):  
J P Fruehauf

The selection of chemotherapy for women with breast or ovarian carcinoma has been traditionally based on results from phase III comparative trials that define the most active drugs and drug combinations. This approach has led to a significant prolongation of the lives of these patients. Unfortunately, few patients with advanced stage IV disease are cured using the currently available regimens. In order to improve the selection process for individual patients, various types of in vitro tests that assess the activity of standard drugs on a patient's tumor have been developed over the past five decades. As with bacterial culture and sensitivity tests, significant predictive correlations between in vitro drug-response assays and cancer patient response and survival have been demonstrated. Medicare currently covers in vitro drug-resistance assays. This review discusses the historical development of in vitro drug-response assays and the clinical validation of various technologies currently available to assist the clinician in selecting the optimal therapy for each patient.


2020 ◽  
Vol 62 ◽  
pp. 85-90
Author(s):  
L. V. Tashmatova ◽  
O. V. Matsneva ◽  
T. M. Khromova ◽  
V. V. Shakhov

The article presents methods of experimental polyploidy of fruit, berry and ornamental plants. The purpose of this review is to highlight the problems and prospects of polyploidization of plants in the open ground and in vitro culture and the possibility of their application for apple trees. For the purpose of obtaining apple tetraploids as donors of diploid gametes, seed seedlings were treated with a solution of colchicine in concentrations of 0.1-0.4 % for 24 and 48 hours. Colchicine concentrations of 0.3 % and 0.4 % at 48 hours of treatment had a detrimental eff ect on their development. As a result, tetraploids and chimeras were obtained from seeds from free pollination of the varieties Orlik, Svezhest, Kandil Orlovsky, as well as from seeds obtained from crossing the varieties Svezhest×Bolotovskoe, Moskovskoe Оzherel’e×Imrus, Girlyanda×Venyaminovskoe. The optimal concentration of colchicine was 0.1 %. Methods of colchicine treatment have been studied: 1) adding to the nutrient medium, colchicine concentration: 0.01%, 0.02%, exposure time 24h-19 days; 2) applying amitotic solution to the growth point, colchicine concentration: 0.1 %, 0.2 %, exposure time 24h-7 days. To increase the penetration of colchicine through the cell walls, a 0.1 % dimexide solution was used. Studies have shown that high concentrations and prolonged exposure to colchicine reduce the viability of explants.


2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.


2020 ◽  
Vol 21 (6) ◽  
pp. 427-435 ◽  
Author(s):  
Cheng Cui ◽  
Siqi Tu ◽  
Valerie Sia Jie En ◽  
Xiaobei Li ◽  
Xueting Yao ◽  
...  

Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information. Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate. Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.


Author(s):  
Giovanni Capovilla ◽  
Renato Salvador ◽  
Luca Provenzano ◽  
Michele Valmasoni ◽  
Lucia Moletta ◽  
...  

Abstract Background Laparoscopic Heller myotomy (HM) has gained acceptance as the gold standard of treatment for achalasia. However, 10–20% of the patients will experience symptom recurrence, thus requiring further treatment including pneumodilations (PD) or revisional surgery. The aim of our study was to assess the long-term outcome of laparoscopic redo HM. Methods Patients who underwent redo HM at our center between 2000 and 2019 were enrolled. Postoperative outcomes of redo HM patients (redo group) were compared with that of patients who underwent primary laparoscopic HM in the same time span (control group). For the control group, we randomly selected patients matched for age, sex, FU time, Eckardt score (ES), previous PD, and radiological stage. Failure was defined as an Eckardt score > 3 or the need for re-treatment. Results Forty-nine patients underwent laparoscopic redo HM after failed primary HM. A new myotomy on the right lateral wall of the EGJ was the procedure of choice in the majority of patients (83.7%). In 36 patients (73.5%) an anti-reflux procedure was deemed necessary. Postoperative outcomes were somewhat less satisfactory, albeit comparable to the control group; the incidence of postoperative GERD was higher in the redo group (p < 0.01). At a median 5-year FU time, a good outcome was obtained in 71.4% of patients in the redo group; further 5 patients (10.2%) obtained a long-term symptom control after complementary PD, thus bringing the overall success rate to 81.6%. Stage IV disease at presentation was independently associated with a poor outcome of revisional LHD (p = 0.003). Conclusions This study reports the largest case series of laparoscopic redo HM to date. The procedure, albeit difficult, is safe and effective in relieving symptoms in this group of patients with a highly refractory disease. The failure rate, albeit not significantly, and the post-operative reflux are higher than after primary HM. Patients with stage IV disease are at high risk of esophagectomy.


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