Ifosfamide And Etoposide Research Articles

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma

The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines. To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma. The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), and 1 to 2 prior lines of systemic treatment. The data analyses were performed between March 22, 2020 (first patient in) and June 22, 2022 (data cutoff for the primary analysis), and September 29, 2023 (end of study final database lock). The OLIE trial assessed the efficacy and safety of lenvatinib (14 mg/m2 taken orally once daily) combined with up to 5 cycles of ifosfamide (3000 mg/m2 intravenously) and etoposide (100 mg/m2 intravenously) on days 1 to 3 of each cycle vs IE alone at the same doses. Patients randomized to IE could cross over to receive lenvatinib upon disease progression by independent imaging review. The primary end point was progression-free survival (PFS) per RECIST 1.1 by independent imaging review. The Kaplan-Meier method was used to estimate the PFS distribution, with a prespecified 1-sided significance threshold of .025 by stratified log-rank test. Secondary end points included PFS rate at 4 months and overall survival. Adverse events were summarized using descriptive statistics. A total of 81 patients were enrolled (median [IQR] age, 15.0 [12.0-18.0] years; 46 males [56.8%]), with 40 in the LEN-IE arm and 41 in the IE arm. Median PFS was 6.5 months (95% CI, 5.7-8.2 months) for the LEN-IE arm and 5.5 months (95% CI, 2.9-6.5 months) for the IE arm (hazard ratio [HR], 0.54; 95% CI, 0.27-1.08; 1-sided P = .04). The rate of PFS at 4 months was 76.3% (95% CI, 59.3%-86.9%) in the LEN-IE arm and 66.0% (95% CI, 47.7%-79.2%) in the IE arm. Median overall survival was 11.9 months (95% CI, 10.1 months to not estimable) with LEN-IE and 17.4 months (95% CI, 14.2 months to not estimable) with IE (HR, 1.28; 95% CI, 0.60-2.70; 1-sided nominal P = .75). Grade 3 or higher treatment-related adverse events occurred in 35 of 39 patients (89.7%) in the LEN-IE arm and 31 of 39 patients (79.5%) in the IE arm. Although LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design. ClinicalTrials.gov Identifier: NCT04154189.

Towards a new era in the treatment of Ewing sarcoma

Although international consensus exists that dose intensification improves outcomes for patients with radiographically localised Ewing sarcoma, treatment strategies to achieve this intensification, and how to translate this improvement to patients with metastatic disease, has remained controversial and enigmatic.1–4 An intercontinental divide for the upfront treatment of Ewing sarcoma has persisted: patients in Europe are most often offered induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), and consolidation with vincristine, actinomycin D, and ifosfamide or cyclophosphamide (VAI or VAC), or busulfan and melphalan (BuMel), whereas in the USA the standard of care consists of interval-compressed cycles of cyclophosphamide, doxorubicin, and vincristine (VDC) plus ifosfamide and etoposide (IE).

Osteosarcoma/Ewing Sarcoma

Osteosarcoma/Ewing Sarcoma

Feasibility and safety of outpatient administration of ifosfamide and etoposide for pediatric patients with Ewing sarcoma in a resource-limited setting amid the COVID-19 pandemic.

BackgroundTo assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource‐limited setting amid the COVID‐19 pandemic.Materials and MethodsRetrospective study of patients with EWS who received outpatient IE from January 2020 until January 2021 at our institution. Ifosfamide 1800 mg/m2 was given for 5 days with MESNA (2‐mercaptoethane sulfonate sodium) infusion and additional boluses before and after 9 hours of hydration. Patients >10 years of age with the ability to drink orally at home, no pre‐existing renal dysfunction or history of hematuria were included. They were monitored for hemorrhagic cystitis with a urine dipstick before, midway, and at end of infusion. A urine analysis was done 24 hours after the last dose of ifosfamide.ResultsForty‐seven (100%) cycles were given as outpatient during the study period. Thirty‐five (74%) cycles were given on time, two (4%) cycles were delayed due to mucositis, two (4%) due to delayed count recovery, and eight (18%) due to unavailability of outpatient appointments. The median interval between these cycles was 15 days (range 14–44 days). No episode of hemorrhagic cystitis was reported. Urine analysis was not done at 24 hours for 27 (58%) cycles, so microscopic hematuria may have been missed. This outpatient protocol saved 32% (USD 299) per cycle in cost and 282 days of hospitalization.ConclusionOutpatient administration of IE for pediatric patients with EWS is feasible, safe, and cost‐effective during the COVID‐19 pandemic.

Apatinib plus ifosfamide and etoposide for relapsed or refractory osteosarcoma: A retrospective study in two centres.

For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1–38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7–18.4) months. The median overall survival time was 19.8 (IQR, 13.1–30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials.

Secondary CIC-rearranged sarcoma responsive to chemotherapy regimens for Ewing sarcoma: A case report.

Capicua transcriptional repressor (CIC)-rearranged sarcoma is an Ewing-like sarcoma with an aggressive clinical course and poor prognosis. No standard treatment has been established. The present study describes a case of CIC-rearranged sarcoma with lung metastases developing in a 24-year-old woman as a therapy-associated malignancy following chemotherapy for anaplastic large cell lymphoma at nine years old. This was treated with palliative regimens used for Ewing sarcoma. The patient achieved disease control for one year. Of note, ifosfamide and etoposide (IE), which were used as a second line treatment lead to a partial response. The case described in the present study indicated that treatment with Ewing regimens is a reasonable option for patients with metastatic CIC-rearranged sarcoma, including those with a second malignant case.

Impact of chemotherapy cycles and intervals on outcomes of nonspinal Ewing sarcoma in adults: a real-world experience

BackgroundAdult Ewing sarcoma (ES) is a rare disease, the optimal treatment model is unknown. This study aimed to retrospectively analyze treatment-related prognostic factors of nonspinal ES in Chinese adults.MethodsEighty-one patients treated between January 2005 and December 2017 were included in the present study. Thirty-three (40.7%) presented with metastatic disease at diagnosis. Eight patients were submitted to primary surgery followed by chemotherapy, while 73 patients received chemotherapy before and after surgery and/or local radiotherapy. The chemotherapy regimen included 8–17 cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) every 3 weeks. Clinical outcomes and safety were analyzed.ResultsVDC/IE chemotherapy was well tolerated in adult patients with ES. Multivariate Cox regression analyses revealed that chemotherapy of at least 12 cycles was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.558; 95% confidence interval, 0.323–0.965; P = 0.037) and overall survival (hazard ratio, 0.424; 95% confidence interval, 0.240–0.748; P = 0.003). Similarly, a low frequency of chemotherapy delays was an independent prognostic factor of improved OS (hazard ratio, 0.438; 95% confidence interval, 0.217–0.887; P = 0.022).ConclusionOur study suggests that adults with ES should be treated with an aggressive multidisciplinary approach, intensive chemotherapy with adequate cycles and appropriate intervals can be recommended in this group.

Feasibility of Treating Adults with Ewing or Ewing-Like Sarcoma with Interval-Compressed Vincristine, Doxorubicin, and Cyclophosphamide Alternating with Ifosfamide and Etoposide

Vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) administered every 2 weeks demonstrated a superior event-free survival compared with 3-week dosing in a landmark pediatric trial and is now standard of care for younger patients. Only 12% of patients enrolled in that trial were over 18 years of age; thus, the feasibility of interval-compressed VDC/IE in adults remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen. Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients with Ewing and Ewing-like sarcoma aged 18 years and older who received VDC/IE every 2 weeks. We identified 24 patients. Median age was 28 years (range 18-60 years). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extraosseous disease. The median interval between cycles was 15.0 days, with no difference between patients aged <30 years versus ≥30 years. The median number of admissions for toxicity per patient was two, primarily for febrile neutropenia. Early treatment discontinuation occurred in 17%. Dose reductions were minimal, with mean cumulative doses achieved comparable to original planned dose and no difference between patients aged <30 years versus ≥30 years. For adults with Ewing and Ewing-like sarcoma, administration of interval-compressed chemotherapy is feasible, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population. For Ewing sarcoma, interval-compressed vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide administered every 2 weeks rather than every 3 weeks has been shown to improve event-free survival in pediatric patients. However, in adults, oncologists may be hesitant to pursue interval-compressed therapy because of concerns for feasibility. In the adult population in this study, a median interval between cycles of 15.0 days (mean 17.0 days) was achieved, comparable to the interval achieved in AEWS0031 (median 15.0, mean 17.3 days). Given that this was achieved without unexpected toxicity or substantial dose reductions and that clinical outcomes were favorable compared with adult historical controls, these results support the use of this regimen in adults.

Abstract 4746: Identifying states of collateral sensitivity during the evolution of therapy resistance in Ewing’s sarcoma

Abstract During the evolution of therapeutic resistance many cancers exhibit a phenomenon termed collateral sensitivity, where resistance to one drug aligns with sensitivity to another drug. It has further been shown, in leukemia and non-small cell lung cancer, that this state of collateral sensitivity can vary over time. We hypothesized that this process will also occur in Ewing’s sarcoma (EWS), and that these phenotypic states can be identified with molecular signatures based on gene expression. The standard chemotherapy for EWS is repeated cycles of two alternating drug cassettes, one is a combination of vincristine, doxorubicin, and cyclophosphamide (VDC), and a second is a combination of ifosfamide and etoposide (IE). This treatment is highly effective, though advanced stage disease often relapses, and then drug resistance invariably develops, a process following the laws of Darwinian evolution. Finding predictable patterns, or signatures, of collateral sensitivity would provide a useful decision support tool in the clinic to help guide chemotherapy choices. Recent studies in other cancers, bacteria, and in silico simulations have explored and identified optimal timing of switching among the drugs of collateral sensitivity to achieving maximal efficacy. To analyze temporal changes in collateral sensitivity in EWS, we exposed two EWS cell lines, A673 and TTC-466, to half maximal inhibitory concentrations of VDC/IE combinations in vitro. As the cultures recovered from drug exposures, we determined their sensitivities against a panel of drugs including the ones used for the treatment and a new generation of drugs that show efficacy against EWS. The new drugs consist of SP2509, pazopanib, olaparib, dactinomycin, temozolomide, vorinostat, and SN-38. We also collected RNA samples to analyze the transcriptomic alterations which correlate with changes in their collateral sensitivity. Significant findings for the A673 cell line include increased resistance to dactinomycin, doxorubicin, etoposide and vincristine for all treatment replicates, and maximal sensitivity to temozolomide halfway through the treatment schedule for all treatment replicates. Notably, every tumor is different and may develop collateral sensitivity at unique time points. Even in this experiment we observe variation between evolutionary replicates that were originally genetically identical. Future work should include investigating a quick and cost-effective method for testing temporal collateral sensitivity of individual tumors so our findings can be implemented clinically. Citation Format: Erin McClure, Masahiro Hitomi, Jessica Scarborough, Jacob Scott. Identifying states of collateral sensitivity during the evolution of therapy resistance in Ewing’s sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4746.

Desmoplastic Small Round Blue Cell Tumor: A Review of Treatment and Potential Therapeutic Genomic Alterations.

Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal translocation. Ewing sarcoma and DSRCT are treated similarly due to similar oncogene activation pathways, and DSRCT has been represented in very limited numbers in sarcoma studies. Despite aggressive therapy, median survival ranges from 17 to 25 months, and 5-year survival rates remain around 15%, with higher survival reported among those undergoing removal of at least 90% of tumor in the absence of extraperitoneal metastasis. Almost 100% of these tumors contain t(11;22) (p13;q12) translocation, and it is likely that EWS-WT1 functions as a transcription factor possibly through WT1 targets. While there is no standard protocol for this aggressive disease, treatment usually includes the neoadjuvant HD P6 regimen (high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV) alternating with ifosfamide and etoposide (IE) chemotherapy combined with aggressively attempted R0 resection). We aimed to review the molecular characteristics of DSRCTs to explore therapeutic opportunities for this extremely rare and aggressive cancer type.

Kidney Cancers in Adolescents &amp; Young Adults

Kidney Cancers in Adolescents &amp; Young Adults

Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

BackgroundChemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group.Patients and methodsAdult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively.ResultsA total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16–75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2–26) was 70% (p < 0.0001). Patients aged 16–40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population.ConclusionsLong-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13569-015-0032-0) contains supplementary material, which is available to authorized users.

Phase I Clinical Trial of Ifosfamide, Oxaliplatin, and Etoposide (IOE) in Pediatric Patients With Refractory Solid Tumors

Oxaliplatin, although related to cisplatin and carboplatin, has a more favorable toxicity profile and may offer advantages in combination regimens. We combined oxaliplatin, ifosfamide, and etoposide (IOE) and estimated the regimen's maximum tolerated dose (MTD) in children with refractory solid tumors. Dose-limiting toxicity (DLT) and MTD were assessed at 3 dose levels in a 21-day regimen: day 1, oxaliplatin 130 mg/m (consistent dose); days 1 to 3, ifosfamide 1200 mg/m/d (level 0) or 1500 mg/m/d (levels 1 and 2) and etoposide 75 mg/m/d (levels 0 and 1) or 100 mg/m/d (level 2). Course 1 filgrastim/pegfilgrastim was permitted after initial DLT determination, if neutropenia was dose limiting. Seventeen patients received 59 courses. Without filgrastim (n=9), DLT was neutropenia in 2 patients at dose level 1. No DLT was observed after adding filgrastim (n=8). There was no ototoxicity, nephrotoxicity >grade 1, or neurotoxicity >grade 2. One patient experienced a partial response and 9 had stable disease after 2 courses. In conclusion, the IOE regimen was well tolerated. Without filgrastim, neutropenia was dose limiting with MTD at ifosfamide 1200 mg/m/d and etoposide 75 mg/m/d. The MTD with filgrastim was not defined due to early study closure. Filgrastim allowed ifosfamide and etoposide dose escalation and should be included in future studies.

Localized Adult Ewing Sarcoma (ES): Improved Outcomes With Ifosfamide and Etoposide (IE) Added to Cyclophosphamide, Doxorubicin, and Vincristine (CAV) Chemotherapy (CT)

Localized Adult Ewing Sarcoma (ES): Improved Outcomes With Ifosfamide and Etoposide (IE) Added to Cyclophosphamide, Doxorubicin, and Vincristine (CAV) Chemotherapy (CT)

SARC006: Phase II trial of chemotherapy in sporadic and neurofibromatosis type 1 (NF1)-associated high-grade malignant peripheral nerve sheath tumors (MPNSTs).

10522 Background: MPNSTs occur in 10% of the NF1 population, and retrospective, pooled analyses have reported worse chemotherapy response for NF1 (9-18%) compared to sporadic MPNSTs (39-55%). Methods: We prospectively evaluated the objective response (OR) rate, [complete responses (CR) and partial responses (PR) WHO criteria] of children and adults with high-grade, unresectable or metastatic chemotherapy naive NF1 associated versus sporadic MPNST after 2 cycles of ifosfamide and doxorubicin (IA) followed by 2 cycles of ifosfamide and etoposide (IE) as primary endpoint. This was followed by surgery and/or radiation for local control and up to 2 more cycles of IA and IE each. Pathology was centrally confirmed. A Simon optimal two-stage design was used with a target response rate of 40% and 17 patients per stratum in the first stage. With 4+/17 ORs, enrollment was to be expanded to 37 patients per stratum, and 11+/37 ORs would be potentially consistent with a 40% OR rate. Results: Both initial stages met criteria for enrollment expansion with 4/17 PRs in NF1 and 4/12 PRs in sporadic MPNSTs, but only 1 additional PR was observed in the expanded NF1 stratum. Of the 9 PRs, 5 were first observed after 2 cycles IA, and additional 4 after 2 cycles IE. Enrollment was slower than expected and the trial was closed before full accrual. Conclusions: While the primary trial objective was not reached due to slow enrollment, with only 5/29 ORs in the NF1 stratum the desired OR rate of 11+/37 would have unlikely been met even if accrual had been completed. We observed a lower OR rate in NF1 compared to sporadic MPNSTs similar to retrospective literature reports. However, our trial was not powered to detect a difference in response rates between the two strata. In addition to PRs after both IA and IE, disease stabilization was achieved in most patients. Novel strategies including the evaluation of targeted agents in combination with chemotherapy should be considered. Clinical trial information: NCT00304083. [Table: see text]

Switching chemotherapy in adult osteosarcoma patients with poor necrosis rates post neoadjuvant methotrexate, cisplatin, and doxorubicin (MAP).

10530 Background: Chemotherapy in the treatment of osteosarcoma has improved 5 year overall survival (OS) from 20% with surgery alone to 60-70%. However, poor tumor necrosis following neoadjuvant chemotherapy (NAC) is associated with decreased survival, therefore strategies to improve outcomes are required for these patients. Methods: Records from all adult patients diagnosed with osteosarcoma between 1986 and 2012 were retrospectively reviewed. Patients were stratified according to age at diagnosis (&lt;40yrs and &gt;40yrs), stage (localised or metastatic) and tumor necrosis post NAC (&lt;90% and &gt;90%). All patients received 2 cycles of methotrexate alternating with cisplatin/doxorubicin (MAP) preoperatively. Following surgery, patients with &gt;90% tumor necrosis continued MAP whilst those with &lt;90% necrosis switched to 4 cycles of ifosfamide and etoposide (IE). Results: 105 patients were identified and 98 who received systemic chemotherapy were included. Median age was 23yrs (Range 15-75yrs); 68% of patients were male. Limb sparing surgery was performed in 76% of applicable patients. Of the patients with localised disease (N=85), 5 year OS, with a median follow up of 8 years (1-26 yrs) was 68% (p=0.002). Patients &lt;40 yrs with localised disease had a 5yr OS of 71% (N=73) compared to 40% in those &gt;40 yrs (N=12) (p=0.05). 2/13 patients with metastatic disease at diagnosis are disease free &gt;10 years post diagnosis. 65 of 73 patients with localised disease &lt; 40 yrs had histology reviewed post neoadjuvant MAP. 34/65 (52%) had &gt;90% tumor necrosis and continued on MAP, 5 yr OS 79%, 31 patients (48%) had &lt;90% necrosis and received adjuvant IE, 5 yr OS 68% (P=0.10). Conclusions: Age and stage are important prognostic factors in patients with osteosarcoma treated with chemotherapy and surgery. Historically, patients with &lt;90% tumor necrosis post NAC are considered to have a poorer prognosis. Switching from MAP to IE is an appropriate salvage regimen in such patients and appears to improve long term survival.

Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

Primitive neuroectodermal tumor (PNET) of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm) on computed tomography (CT) was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen), vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE). This is the first report of adrenal peripheral PNET (pPNET) from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study

The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue. Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks. Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites. Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

Dose‐escalated CHOP and tailored intensification with IFE according to early response and followed by BEAM/autologous stem‐cell transplantation in poor‐risk aggressive B‐cell lymphoma: a prospective study from the GEL–TAMO Study Group

The role of high-dose therapy and autologous stem-cell transplantation (HDT/ASCT) in the up-front treatment of poor-risk aggressive lymphoma is still unknown. We conducted a prospective multi-centre trial with dose-escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT according to early response assessed by CT and gallium scan (Ga67S). Eighty-six patients with newly diagnosed and Ga-67 avid aggressive B-cell lymphoma received MegaCHOP for three courses and were evaluated for response by CT and Ga67S. Patients with CT response and negative Ga67S received another MegaCHOP cycle followed by BEAM and ASCT. Those patients with positive Ga67S or without CT response received salvage treatment with two courses of ifosfamide and etoposide (IFE) followed, whenever response had been achieved, by BEAM and ASCT. Response rate before HDT/ASCT was 85% and, with 34 months of median follow-up, progression-free survival (PFS), overall survival (OS) and treatment-related mortality were 56%, 64% and 7%, respectively. For transplanted patients (81% of the whole series), PFS and OS were 67% and 74%, respectively. No different outcomes were observed between patients achieving an early negative Ga67S response treated with MegaCHOP and BEAM/ASCT and patients with mid-treatment positive Ga67S who received IFE prior BEAM/ASCT. This response-adapted strategy including early treatment modifications prior HDT/ASCT have yielded encouraging PFS and OS in patients with poor-risk B aggressive non-Hodgkin's lymphoma.

Radiographic tumor response in pediatric patients with newly diagnosed localized (LOC) or metastatic (MET) Ewing’s sarcoma (EWS) following neoadjuvant chemotherapy

20008 Background: Standard treatment for EWS includes vincristine, doxorubicin, cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE). Using this therapy, overall survival is 70% in patients with LOC EWS and 30% in patients with MET EWS. We compared the radiographic response to VDC and IE in patients with LOC or MET EWS. Methods: We conducted a randomized trial comparing pegfilgrastim to filgrastim in patients treated with VDC (cycles 1, 2, 5, 9, 11, 13) and IE (cycles 3, 4, 6–8, 10, 12, 14). Local control with radiation or surgery was initiated after cycle 5. We assessed radiographic response after VDC (C1,2) and IE (C3,4) using 1-dimensional (RECIST) and 2-dimensional (WHO) criteria. Measurements were performed using MEDx. Results: Twenty-one patients with EWS, median age 20y (6–25y), were enrolled; 16 were evaluable for this analysis. Primary tumors were in extremity (n=5) or central axis (n=11). Eight patients had MET disease (pulmonary only, n=4). Median (range) decrease in tumor size by WHO after C4 was 61% (40–92%) for LOC and 83% (47–94%) for MET. Decrease by treatment is presented in the table . Overall responses after 4 cycles for LOC patients were 5 PR, 3 SD using RECIST, and 6 PR, 2 SD using WHO. For MET patients, overall responses were the same using RECIST and WHO, 7 PR, and 1SD. Conclusion: Patients with MET EWS responded as well as those with LOC EWS after 4 cycles of neoadjuvant chemotherapy. Similar overall response was demonstrated using RECIST or WHO. Tumor response after VDC was greater than after IE, possibly due to sequence of administration, but patients had continued tumor response with IE. [Table: see text] No significant financial relationships to disclose.