The first line systemic chemotherapy in metastatic gastric carcinoma: A comparison of docetaxel, cisplatin and fluorouracil (DCF) versus cisplatin and fluorouracil (CF); versus epirubicin, cisplatin and fluorouracil (ECF) regimens in clinical setting.

BACKGROUND/AIMS: This study evaluated the efficacy and safety of the first-line chemotherapy regimens in advanced gastric carcinoma (AGC). METHODOGY: In this study, 116 patients who had advanced stage gastric adenocarcinoma were evaluated. The patients receiving Cisplatin/5-Flourouracil (CF) regimen (n=36) were compared with either those receiving Epirubicin/Cispatin/5-Flourouracil (ECF) regimen (n=40) or those receiving Docetaxel/Cispatin/5-Flourouracil (DCF) regimen (n=40). RESULTS: The overall response rate (ORR) was 18%, 30%, and 40% with CF, ECF, and DCF, respectively. Progression-free survival (PFS) was 4.3, 4.4 and 5.8 months for CF, ECF and DCF, respectively. Although overall survival was similar in all 3 groups, 1-year and 2-year survival rates were better on DCF group compared to the other two groups. CONCLUSION: The results of our study suggest that DCF is superior in terms of ORR and PFS in comparison to CF and ECF combinations in AGC.

High complete remission rate and durable remissions achieved with rational use of autologous stem-cell transplantation, thalidomide maintenance, and non-myeloablative allogeneic transplantation in patients with multiple myeloma.

Autologous stem-cell transplantation (ASCT) has emerged as the standard approach in patients with multiple myeloma, although it is unlikely to achieve cure. Thalidomide maintenance and non-myeloablative allogeneic transplantation (NST) may increase complete remission (CR) rate and increase overall survival. In this study, 35 ASCT and 10 NST were performed in 33 patients. Patients, who were resistant or relapsed following ASCT, underwent NST if they had an HLA-matched sibling, otherwise treated with a second ASCT. Thalidomide was started as maintenance after ASCT. After first transplantation, three patients underwent second ASCT and 10 patients underwent NST. Following first transplantation, CR rate was 39% and increased to 60% (overall response 93%) with addition of thalidomide, bortezomib, and second transplantation. CR was durable in 14 (42%) patients. During a median follow-up of 24 months, 18 patients progressed and nine patients died. The 100-d transplant-related mortality was <5%. The four-yr progression-free survival (PFS) was 52.4%. In conclusion, ASCT followed by thalidomide and NST in resistant patients can lead to high CR and PFS rates. As a second transplantation has not been performed routinely, patients having durable CR had a chance to avoid or delay a second transplantation without compromising disease control.

Characteristics of breast cancer patients with central nervous system metastases: a single-center experience.

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Thymic epithelial neoplasia: a study of 58 cases.

Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 +/-13.8 yr (range, 17-73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty-five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p> 0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival.

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma.

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Hypocalcemic effect of zoledronic acid or other bisphosphonates may contribute to their antiangiogenic properties.

Bisphosphonates, effectively used for metastatic bone disease and hypercalcemia, may evidentially have antiangiogenic properties. However, mechanism(s) of antiangiogenic effects of bisphosphonates are not fully understood. Their most pronounced effect is on metabolism of calcium, which is a main point of intersection for many distinct molecular signaling pathways that promote and modulate angiogenesis. An elevation of Ca(2+) plays a role in the mitogenic and secretory effects of growth factors. Some preclinical clues imply that antiangiogenic effects of bisphosphonates are related to its well-known hypocalcemic activity. Consequently, it may not be right to routinely recommend vitamin D and calcium supplementation to correct hypocalcemia unless it is symptomatic.

Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists.

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.

Paclitaxel and doxorubicin combination in the first-line treatment of metastatic breast cancer.

Anthracyclines and taxanes are currently the most effective drugs in the treatment of metastatic breast carcinoma. The aim of this study was to determine the efficacy and toxicity of paclitaxel and doxorubicin combination in the first-line treatment of metastatic breast cancer. Forty-five women with metastatic breast cancer were recruited in the study. Median age was 49 years (range, 33-70). Treatment protocol: doxorubicin (50 mg/m2/day, 30-min infusion) followed by paclitaxel (200 mg/m2/day, 3-hr infusion) every 3 weeks. Response rates included complete response in 13 (28.9%) patients and partial response in 19 (42.2%) patients, with an overall response rate of 71%. Five (11%) patients had stable disease and 8 (18%) patients had progressive disease. At a median follow-up of 19.7 months, median time to progression for all patients was 19.9 months (95% confidence interval, 12.8 to 27 months). Median overall survival time was 28.4 months. Grade 3-4 nausea/vomiting and hematological toxicities were observed in 12 (26%) and 6 (13.3%) patients, respectively. Cardiac toxicity was observed in 2 (4.4%) patients. In this trial, paclitaxel and doxorubicin combination was demonstrated to be a favorable and active regimen in the first-line treatment of metastatic breast cancer.

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors.

AIMS AND BACKGROUND: We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. METHODS: A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. RESULTS: A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. CONCLUSIONS: We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

Neoadjuvant chemotherapy with taxotere-epirubicin-5-fluorouracil (TEF) in local-regionally advanced breast cancer: a preliminary report.

AIMS AND BACKGROUND: Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). METHODS AND STUDY DESIGN: Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. RESULTS: Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25-77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 +/- 6.8 (range, 3.5-28) months and the mean overall survival was 18.6 +/- 7.2 (range, 5-30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. CONCLUSIONS: TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.

Clinical Features and Prognostic Factors of Hodgkin's Lymphoma: A Single Center Experience.

BACKGROUND: Hodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. AIMS: We designed a retrospective study to investigate the clinical features and prognostic factors of HL patients diagnosed at an experienced oncology centre. STUDY DESIGN: Retrospective study. METHODS: Demographic characteristics, histopathological and clinical features, treatment modalities and response to treatment were obtained from hospital records. Dates of initial diagnosis, remission and relapse, last visit and death were recorded for survival analyses. RESULTS: We analysed data of 391 HL patients (61% male, 39% female; mean age 35.7±15.1 years). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (42.7%). The most common stage was II 50.4%. The most common chemotherapy regimen was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (70.6%). Five and 10-year survival rates were 90% and 84%, respectively. Early-stage patients with good prognostic factors had better overall and relapse-free survival rates. The presence of "B" symptoms, albumin level, Eastern Cooperative Oncology Group (ECOG) performance score, and LDH were prognostic factors that affect the survival in both univariate and multivariate analyses. CONCLUSION: This is the first study that demonstrates the demographic, clinical and prognostic features of HL patients in Turkey, and provides a general picture of the HL patients in our country.

Long-term complications in Hodgkin's lymphoma survivors.

Background. Although patients with Hodgkin's lymphoma (HL) achieve prolonged survival, long-term complications are a major cause of morbidity and mortality among long-term survivors of HL. Methods. We retrospectively evaluated long-term complications in 336 HL survivors treated between January 1990 and January 2006 at the Department of Medical Oncology of the Hacettepe University Institute of Oncology who were >16 years old at presentation. All patients were regularly followed up every 3 months for the first 2 years after complete response, biannually for 3 years, and annually after 5 years. Results. Median follow-up was 8.5 years. The mean age (±SD) of the patients at the time of diagnosis was 35.7 ± 13.1 years. The male to female ratio was 61%/39%. During follow-up, 29 second malignancies (8.6%) were diagnosed in 28 patients with HL; 22 were solid tumors and 7 were hematological malignancies. Forty-seven (14.0%) of all patients with HL were found to have thyroid abnormalities. During follow-up, 54 (16.1%) patients developed cardiovascular complications. Overall, 29 (8.6%) patients developed late pulmonary toxicities. The cumulative number of chronic viral infections was 13 (3.9%). Conclusions. Long-term survivors of HL need to be properly followed up not only for disease control but also for evaluation of possible late morbidities to minimize the consequences.

Early and late arrhythmogenic effects of doxorubicin.

BACKGROUND: To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens. PATIENTS AND METHODS: A prospective study including 29 patients who were treated with doxorubicin-containing regimens. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens, as well as after the last cycle of chemotherapy. RESULTS: The mean age of the patients was 45.8 +/- 15.1 (range 18-69). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%) and in 18 (62.1%) patients after completion of therapy. One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated. The patient subsequently underwent permanent pacemaker implantation. CONCLUSIONS: Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated.

Expression of PTEN, cyclin D1, P27/KIP1 in invasive ductal carcinomas of the breast and correlation with clinicopathological parameters.

In this study, tumour tissue samples of 85 primary breast cancer patients were evaluated for phosphatase and tensin homolog deleted on chromosome ten (PTEN), cyclin D1 and P27/Kip1 expression patterns. The results were correlated with clinicopathological parameters. Loss of PTEN protein expression was present in 32.5% of the cases. Cyclin D1 was overexpressed in 54.2% and P27/Kip1 in 89.3% of the cases. Statistically significant associations were found between PTEN and cyclin D1 expression patterns, and cyclin D1 expression and tumour size.

Nonconvulsive status epilepticus due to ifosfamide.

OBJECTIVE: To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. CASE SUMMARIES: Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. DISCUSSION: The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. CONCLUSIONS: Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

Ifosfamide, idarubicin, and etoposide in relapsed/refractory Hodgkin disease or non-Hodgkin lymphoma: a salvage regimen with high response rates before autologous stem cell transplantation.

To achieve long-term disease-free survival, high-dose therapy and autologous stem cell transplantation (ASCT) is the current standard approach in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL). Because chemosensitivity is a significant factor in determining transplantation eligibility, it is critical to select a salvage chemotherapy regimen that has the potential to induce a high response rate with low nonhematologic toxicity. In this phase II study, 49 patients with relapsed or refractory HD (n = 22) and NHL (n = 27) with a median age of 42 years were treated with an IIVP salvage regimen consisting of ifosfamide, idarubicin, and etoposide. Twenty-seven percent of the patients had primary refractory disease, whereas 22% and 51% had early and late relapses, respectively. As analyzed by intention to treat, 16 patients (33%) achieved complete remission and 21 patients (43%) achieved a partial response, leading to an overall response rate of 76% (63% in NHL and 91% in HD). In the univariate analysis, diagnosis (HD versus NHL), remission duration before the initiation of IIVP, disease bulk, increased lactate dehydrogenase, and the presence of "B" symptoms were significant factors affecting the response achieved by the IIVP regimen. Of 37 responders, 31 (84%) underwent high-dose therapy and transplantation. The probability of 4-year overall survival (OS) and event-free survival (EFS) in this group of patients who underwent ASCT was 67.7% and 49.1%, respectively. When compared with the patients who achieved a partial response, patients who achieved complete remission with the IIVP regimen had a significantly higher probability of 4-year EFS (67.3% versus 30%; P = .016) and 4-year OS (92.3% versus 39.2%; P = .003). In patients with HD, 4-year EFS and 4-year OS were 54.9% and 70.6%, respectively, without a significant difference with respect to the survival rates obtained in patients with NHL (43.6% and 63.6%, respectively). Common side effects observed during 102 cycles of therapy were grade 3 to 4 neutropenia (62%) and thrombocytopenia (58%). The IIVP regimen is a highly effective salvage regimen for patients with relapsed or refractory HD or NHL who are candidates for ASCT. Furthermore, the degree of response to IIVP predicts the posttransplantation outcome. However, close follow-up is necessary because of a high incidence of grade 3 to 4 hematologic toxicity.

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.