Successful Treatment of Three Cases of Generalized Pustular Psoriasis With Granulocyte and Monocyte Adsorption Apheresis

Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life‐threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.     

Interferon treatment of refractory idiopathic thrombocytopenic purpura (ITP)

Abstract: Up to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are refractory to standard therapy with corticosteroids and splenectomy. The treatment of refractory ITP is barely effective, but promising results of interferon therapy were reported recently. In a prospective study 21 refractory ITP patients were treated with interferon alpha 2B at 3 million Units three times a week for a period of 4 weeks. Ten out of 21 patients had a response, of whom 2 had a complete response of 3.5 and 7 months duration, after which both relapsed. One other patient retreated after relapse has a complete response of 24 + months. The characteristics of the responding patients were not different from the non-responding patients. Adverse effects were minimal. Short treatment with interferon in refractory ITP patients may be justified and the results reported here challenge us to elucidate the mechanism of action of interferon.     

Generalized pustular psoriasis successfully treated with granulocyte and monocyte adsorption apheresis

Generalized pustular psoriasis (GPP) is one of the neutrophilic dermatoses mainly caused by activated neutrophils and monocytes. Granulocyte and monocyte adsorption apheresis (GCAP) is a useful extracorporeal circulation therapy for removal of activated granulocytes and monocytes. In this study, GCAP was used to treat three patients with different types of GPP; the diagnoses indicated patient 1 had GPP, patient 2 had GPP developed from psoriasis vulgaris and patient 3 had GPP based on psoriatic erythroderma. We performed GCAP on each of these patients once a week, for a total of five times. We found that the patients' pustules and edema disappeared and their erythema was reduced by GCAP therapy. Moreover, no adverse effects were observed. Thus, we conclude GCAP could be effective for treating various types of GPP.     

Intensive granulocyte and monocyte adsorption versus intravenous prednisolone in patients with severe ulcerative colitis: An unblinded randomised multi-centre controlled study

BACKGROUND AND AIM: Several uncontrolled studies have reported on the efficacy of adsorptive depletion of peripheral blood granulocytes and monocytes/macrophages (GM) in patients with moderate or severe ulcerative colitis. This study was to compare the efficacy and safety of intensive GMA with intensive intravenous prednisolone in patients with severe ulcerative colitis. METHODS: Seventy patients with clinical activity index 10-23 were randomly assigned to intensive GMA with the Adacolumn, at 2 sessions/week in the first 3 weeks and then 1 session/week for up to 11 sessions (n = 35) or intravenous prednisolone, 40-60 mg/day for 5-10 days (n = 35). No patient received immunomodulators within 8 weeks prior to entry. Clinical response based on intention to treat was assessed at weeks 2, 6 and 12. RESULTS: Four patients in the prednisolone group and two patients in the GMA group discontinued in week 1. At weeks 2, 6 and 12, the remission (clinical activity index < or = 4) rates (%) in the GMA group were 17.1, 54.4, 74.3, respectively. The corresponding values in the prednisolone group were 25.7, 51.4 and 48.6. Further, at week 12, 27 patients (77%) in the GMA group and 5 patients (14%) in the prednisolone group were steroid free (P = 0.0076). In the GMA group, flushing and light-headedness were observed in 5 patients versus typical steroid side effects in 29 patients of the prednisolone group. CONCLUSIONS: In this clinical response to GMA was comparable or better than prednisolone. Further, the response to GMA was slower than to intravenous prednisolone, but was more sustainable than the latter.     

Granulocyte and monocyte adsorptive apheresis for patients with chronic hepatitis C virus infection: a report on six cases with high plasma viremia

Abstract: Granulocytes and monocytes/macrophages (GM) are known to constitute extra‐hepatic sites for hepatitis C virus (HCV) replication and dissemination. Accordingly, we thought that selective GM adsorptive apheresis (GMA) might contribute to the treatment of HCV in patients with high viremia (HCV‐RNA > 100 kIU/mL). Of six patients (three males and three females), mean age 62.2 years, five had not responded to interferon‐α (INF‐α) and one was INF‐α naïve. Each patient received five GMA sessions, once a week for 5 weeks. The two antecubital veins were used as blood access and return lines and the apheresis was performed at 30 mL/min for 60 min. Treatment efficacy was assessed by monitoring changes in plasma HCV‐RNA and aminotransferase. Granulocyte and monocyte/macrophage adsorptive apheresis was well tolerated. During each GMA, there was on average a 52.9% fall in plasma HCV‐RNA, but HCV‐RNA increased again during the time before the next GMA. There was no marked change in either aminotransferase during GMA. Furthermore, beyond the last GMA, HCV‐RNA increased together with worsening aminotransferase in three of six patients. In conclusion, it would appear that GMA can partially reduce plasma HCV and GMA at a frequency of one session/week for 5 consecutive weeks but that this was inadequate to induce a sustained decrease in plasma HCV‐RNA in patients with high viremia without simultaneous administration of antiviral medications. The most effective frequency of GMA needs to be determined in future clinical studies.     

Phase I study of continuous-infusion PALA and 5-FU

Eighteen patients with malignancies refractory to conventional forms of therapy were treated with 5-day continuous infusions of PALA and 5-FU. PALA was administered at a dose of 940 mg/m2/day. 5-FU was initially given at a dose of 180 mg/m2/day and was incrementally increased to 325 mg/m2/day. The courses were repeated every 3-4 weeks. Mucositis and diarrhea were the dose-limiting toxic effects. Other reversible side effects included grade 2 skin rashes and nausea and vomiting. Peak plasma PALA concentrations were approximately 20 microM and occurred in conjunction with a maximum depression of leukocyte-L-aspartate transcarbamylase (ATCase) activity to 10% of baseline. Therapeutic responses occurred in one of the 13 patients with colon carcinoma and in one patient with mammary carcinoma. Responses could not be correlated with leukocyte ATCase depression. Recent data indicate that low doses of PALA (250 mg/m2) might be equally as effective in inhibiting leukocyte ATCase activity as the doses used in this study. A phase II trial has been designed at this institution employing the above doses of PALA in conjunction with escalating doses of 5-FU.     

Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease

Background

Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn^®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity.

Methods

Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months.

Results

Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time.

Conclusions

IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.

     

Twenty-four-week follow-up examination of a leukocytapheresis therapy in rheumatoid arthritis

Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe and effective therapy for patients with refractory rheumatoid arthritis (RA). However, most of those reports were limited to short-term clinical observation. We have treated 11 RA patients with LCAP and observed them for 24 weeks after the final administration. The 11 cases included 3 diabetes patients, 2 patients with interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient with old pulmonary tuberculosis. Alternative therapies for all of these patients were considered difficult. Once-a-week LCAP administration was added for 5 weeks to the previous therapeutic regime in all patients, and the treatment efficacy was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11 patients (73%) had achieved an American College of Rheumatology (ACR) 20% response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses. Although the efficacy decreased after the observation periods, an ACR 20% response was maintained in 5 patients (45%) at 24 weeks. Although only a limited number of patients were examined in this study, the results suggested that LCAP therapy will be beneficial to RA patients, including patients who cannot be treated with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs.     

Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel disease

BACKGROUND: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. METHODS: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered t an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5-10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). RESULTS: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35-203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. CONCLUSION-: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted.     

Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia

This open-label, dose-escalation study evaluated the safety and efficacy of single-agent gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted chemotherapeutic agent, for pediatric patients with multiple relapsed or primary refractory acute myeloid leukemia (AML). Twenty-nine children 1 to 16 years of age (relapsed disease, 19; refractory disease, 10) received gemtuzumab ozogamicin ranging from 6 to 9 mg/m2 per dose for 2 doses (separated by 2 weeks) infused over 2 hours. All patients had anticipated myelosuppression. Other toxicities included grade 3/4 hyperbilirubinemia (7%) and elevated hepatic transaminase levels (21%); the incidence of grade 3/4 mucositis (3%) or sepsis (24%) was relatively low. One patient treated at 9 mg/m2 developed veno-occlusive disease (VOD) of the liver and defined the dose-limiting toxicity. Thirteen patients underwent hematopoietic stem-cell transplantation less than 3.5 months after the last dose of gemtuzumab ozogamicin; 6 (40%) developed VOD. Eight of 29 (28%) patients achieved overall remission. Remissions were comparable in patients with refractory (30%) and relapsed (26%) disease. Mean multidrug resistance-protein-mediated drug efflux was significantly lower in the leukemic blasts of patients achieving remission (P < .005). Gemtuzumab ozogamicin was relatively well tolerated at 6 mg/m2 for 2 doses and was equally effective in patients with refractory and relapsed disease. Further studies in combination with standard induction therapy for childhood AML are warranted.     

Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes

OBJECTIVES: An open study of B-lymphocyte depletion was undertaken in rheumatoid arthritis (RA) patients to test the hypothesis that B lymphocytes may be essential to disease perpetuation. METHODS: Five patients with refractory RA were treated with a monoclonal anti-CD20 antibody, cyclophosphamide and prednisolone and followed for 12-17 months. Patient 2 received further treatments at 8 and 12 months and patient 4 at 11 months. RESULTS: At 26 weeks all patients satisfied the American College of Rheumatology ACR50 and patients 1-3 the ACR70 criteria of improvement, without further therapy. Patients 1, 3 and 5 achieved ACR70 at 1 yr and rheumatoid factor (RF) levels fell to normal. In patients 3 and 5, B lymphocytes returned without relapse. Patient 2 relapsed at 28 weeks and patient 4 at 38 weeks, coincident with the return of B lymphocytes in the presence of raised RF levels. Both achieved ACR70 on retreatment. Adverse events were limited to respiratory episodes (two patients) and marginal thrombocytopenia (one patient). CONCLUSIONS: These findings are consistent with the concept that RA is critically dependent on B lymphocytes and suggest that B-lymphocyte depletion may be a safe and effective therapy.     

Twenty-four-week follow-up examination of a leukocytapheresis therapy in rheumatoid arthritis

Abstract

Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe and effective therapy for patients with refractory rheumatoid arthritis (RA). However, most of those reports were limited to short-term clinical observation. We have treated 11 RA patients with LCAP and observed them for 24 weeks after the final administration. The 11 cases included 3 diabetes patients, 2 patients with interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient with old pulmonary tuberculosis. Alternative therapies for all of these patients were considered difficult. Once-a-week LCAP administration was added for 5 weeks to the previous therapeutic regime in all patients, and the treatment efficacy was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11 patients (73%) had achieved an American College of Rheumatology (ACR) 20% response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses. Although the efficacy decreased after the observation periods, an ACR 20% response was maintained in 5 patients (45%) at 24 weeks. Although only a limited number of patients were examined in this study, the results suggested that LCAP therapy will be beneficial to RA patients, including patients who cannot be treated with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs.     

Efficacy of granulocyte and monocyte adsorption apheresis for three cases of refractory pyoderma gangrenosum

Pyoderma gangrenosum presents with chronic skin ulcers and is histologically characterized by neutrophil infiltration throughout the dermis. It is also occasionally associated with ulcerative colitis, a type of inflammatory bowel disease, against which granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable efficacy. We performed GCAP on three refractory cases of pyoderma gangrenosum with painful bilateral leg ulcers and hereby report the results obtained. Patient 1 was a 43-year-old woman with a four-year history of recurrent painful skin ulcers treated with prednisolone and cyclosporine. Patient 2 was a 29-year-old woman who had been suffering from pyoderma gangrenosum with severe pain for two weeks, associated with an 11-year history of ulcerative colitis treated with prednisolone and salazosulfapyridine. Patient 3 was a 63-year-old man with a three-year history of recurrent ulcers with pain, suffering from rheumatoid arthritis treated with prednisolone and cyclophosphamide. The sizes of the lesions were reduced in all three patients following a weekly GCAP treatment for 10 or 11 consecutive weeks, and the re-epithelialization of ulcers were additionally observed in two patients. The pain disappeared dramatically in all three patients following two sessions of GCAP therapy. No adverse effects were observed for up to at least eight months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, with regards to refractory cases of pyoderma gangrenosum.     

Treatment of refractory Crohn's disease by intensive granulocyte and monocyte adsorption apheresis: a report on two drug refractory cases

Granulocyte and monocyte adsorption apheresis (GMA) is one therapeutic option for induction of remission in patients with inflammatory bowel diseases. Recently intensive GMA (2 sessions per week) was reported to be strikingly better than weekly GMA, both in remission rate and time to remission. Here we report two cases of Crohn's disease refractory to weekly GMA who responded to intensive GMA. One patient had not received immunosuppressive therapy while the other had been refractory to combination therapy with infliximab and azathioprine. Intensive GMA induced remission in these 2 patients. Intensive GMA may represent a therapeutic choice for remission induction and maintenance with infliximab.     

Adsorptive Granulocyte/Monocyte Apheresis for the Maintenance of Remission in Patients with Ulcerative Colitis: A Prospective Randomized, Double Blind, Sham-Controlled Clinical Trial

Background/Aims

Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse.

Methods

Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks.

Results

At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups.

Conclusions

Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.     

Treatment of hairy cell leukemia with recombinant alpha 2 interferon

Nine patients with progressive hairy cell leukemia were treated with subcutaneous injections of recombinant alpha 2 interferon (2 to 10 X 10(6) U/m2) three times weekly. Eight patients completed at least eight weeks of treatment and were evaluable; one patient with refractory thrombocytopenia died of an intracerebral hemorrhage after two doses of interferon. Seven of eight patients responded, with responses occurring as early as two weeks. Four patients also had resolution of their monocytopenia. No complete responses were seen with up to 30 weeks of treatment. Bone marrow biopsies demonstrated improvement in all eight patients. No unforeseen toxicity occurred, but most patients had transient myelosuppression during the first few weeks of treatment. Recombinant alpha 2 interferon is effective in the treatment of hairy cell leukemia, with acceptable toxicity.     

Thalidomide therapy in patients with refractory or relapsed multiple myeloma

We treated seven refractory or relapsed myeloma patients resistant to conventional chemotherapy with thalidomide. We started thalidomide at 100 mg daily and the dose was increased up to 300 mg if the patient could tolerate it. The patients were evaluated at four weeks and 12 mg of dexamethasone was added for four days when the patient failed to respond to thalidomide treatment. One patient was excluded from the study because of general fatigue. Two of the six patients responded to thalidomide alone and three of the remaining four patients responded to the combination with dexamethasone. The most common adverse effect was sleepiness which was seen in three patients. Two patients showed pancytopenia (Grade 3), constipation and skin eruption. Of the six patients four needed reduction of the thalidomide dose to 200 mg because of adverse effects. Plasma levels of TNF-alpha, IL-6, bFGF and VEGF were measured before and after four weeks. High plasma bFGF levels were seen in responding patients. In conclusion, treatment with thalidomide alone or in combination with dexamethasone is feasible and effective in refractory or relapsed myeloma patients. Further study is required to clarify the role of thalidomide in the therapeutic strategy for multiple myeloma.     

Effects of plasma exchange (PE) in primary biliary cirrhosis (PBC). A pilot study

Six patients were studied to evaluate the efficacy and safety of plasma exchange (PE) in the treatment of primary biliary cirrhosis (PBC). All patients were affected by PBC at stage III-IV and presented symptoms refractory to pharmacologic therapy. Patients underwent PE for a mean period of 40 weeks (range 10-88). A mean of 33 liters (range 17-64) of plasma per patients was removed. Patients reported less fatigue (4/6), pruritus (5/5), nausea (3/3), Sjogren's syndrome (2/6), and painful neuropathy (2/3). A reduction of xanthomata was noted in one of the three affected patients. Definitive improvement was seen in the patient with Raynaud's phenomenon. A significant reduction was noted for serum cholesterol and gammaglobulins. ALT, AST, gamma-GT, alkaline phosphatase, bilirubin, prothrombin activity, AMA titers were not affected by PE. All patients suffered some mild adverse effects during PE. Two patients (IV stage) developed late edema and ascites after 34 and 44 weeks of treatment. We conclude that PE can be considered effective chronic treatment for advanced symptomatic PBC refractory to pharmacological therapy.     

Pilot feasibility studies of leukocytapheresis with the Adacolumn Apheresis System in patients with active ulcerative colitis or Crohn disease

GOALS: Two uncontrolled, multicenter feasibility studies evaluated safety and pilot efficacy of selective granulocyte and monocyte adsorption apheresis (GMA) with the Adacolumn Apheresis System for treatment of moderate-to-severe ulcerative colitis (UC) and Crohn disease (CD) patients refractory/intolerant to conventional pharmacologic therapy. BACKGROUND: Patients with UC and CD, characterized by elevations in peripheral blood granulocytes, monocytes/macrophages, and proinflammatory mediators, may benefit from reductions in activated granulocytes and monocytes by selective apheresis. METHODS: Patients underwent weekly Adacolumn sessions for 5 weeks. Pilot efficacy assessments used disease activity index (DAI) for UC (0-12) or CD activity index (CDAI; 0-600) for CD. RESULTS: Eleven of 15 UC patients completed all 5 treatments. Mean DAI scores fell from 8.4+/-1.3 (baseline) to 5.2+/-2.9 (week 7). Five patients had DAI reductions of > or = 3 points at week 7. Fourteen of 15 CD patients completed all 5 treatments. Mean CDAI scores fell from 308.0+/-76.5 (baseline) to 200.6+/-117.4 (week 7). Nine CD patients responded (CDAI reductions > or = 70 points) at week 7. Remission (CDAI score < or = 150 at week 7) was observed in 6 patients. There were no device-related serious adverse effects. CONCLUSIONS: Treatment with Adacolumn may be feasible and effective in patients with moderate-to-severe refractory inflammatory bowel disease. Larger sham-controlled studies are ongoing.     

Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5‐fluorouracil for locally advanced esophageal cancer

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5‐fluorouracil (5‐FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5‐FU. The main treatment‐related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1–2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3–4, 53% of the patients experienced grade 1–2 mucositis, and 40% experienced grade 1–2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3–4 dysphagia in weeks 3–4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1–2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1–2 dysphagia and 26% patients experienced grade 3–4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2‐year disease‐free survival was 53%. The median survival was 3.2 years with the 2‐year overall survival of 73%. Preoperative oxaliplatin/5‐FU‐based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.