bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of molecular monitoring during the treatment of chronic myeloid leukemia: a Cancer and Leukemia Group B study.
Authors: Stock W , Westbrook C A , Peterson B , Arthur D C , Szatrowski T P , Silver R T , Sher D A , Wu D , Le Beau M M , Schiffer C A , Bloomfield C D
Published: February 2017

PURPOSE

Disappearance of the Philadelphia chromosome during treatment for chronic myeloid leukemia (CML) has become an important therapeutic end point. To determine the additional value of molecular monitoring during treatment for CML, we performed a prospective, sequential analysis using quantitative Southern blot monitoring of BCR gene rearrangements of blood and marrow samples from Cancer and Leukemia Group B (CALGB) study 8761.

PATIENTS AND METHODS

Sixty-four previously untreated adults with chronic-phase CML who were enrolled onto CALGB 8761, a molecular-monitoring companion study to a treatment study for adults with chronic-phase CML (CALGB 9013). Treatment consisted of repetitive cycles of interferon alfa and low-dose subcutaneous cytarabine. Blood and marrow Southern blot quantitation of BCR gene rearrangements was compared with marrow cytogenetic analysis before the initiation of treatment and of specified points during therapy. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was performed to detect residual disease in patients who achieved a complete response by Southern blot or cytogenetic analysis.

RESULTS

Quantitative molecular monitoring by Southern blot analysis of blood samples was found to be equivalent to marrow monitoring at all time points. Twelve of 62 (19%) follow-up samples studied by Southern blot analysis had a complete loss of BCR gene rearrangement in matched marrow and blood specimens. Southern blot monitoring of blood samples was also found to be highly correlated to marrow cytogenetic evaluation at all points, although there were four discordant cases in which Southern blot analysis of blood showed no BCR gene rearrangement, yet demonstrated from 12% to 20% Philadelphia chromosome-positive metaphase cells in the marrow. RT-PCR analysis detected residual disease in five of six patients in whom no malignant cells were detected using Southern blot or cytogenetic analyses.

CONCLUSION

Quantitative Southern blot analysis of blood samples may be substituted for bone marrow to monitor the response to therapy in CML and results in the need for fewer bone marrow examinations. To avoid overestimating the degree of response, marrow cytogenetic analysis should be performed when patients achieve a complete response by Southern blot monitoring. This approach provides a rational, cost-effective strategy to monitor the effect of treatment of individual patients, as well as to analyze large clinical trials in CML.
Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma.
Authors: Smith T J , Hillner B E , Schmitz N , Linch D C , Dreger P , Goldstone A H , Boogaerts M A , Ferrant A , Link H , Zander A , Yanovich S , Kitchin R , Erder M H
Published: February 2017

PURPOSE

High-dose chemotherapy (HDC) with peripheral-blood progenitor cell (PBPC) and autologous bone marrow (ABM) transplant (T) has documented survival benefits for relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Treatment costs associated with HDC and its supportive care have restricted its use both on and off clinical trial. In a prospective randomized clinical trial, filgrastim-mobilized PBPCT resulted in faster recovery of bone marrow function, with less hospitalization and supportive care than ABMT. This study was undertaken to analyze the costs of the two strategies using prospectively collected data from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT.

PATIENTS AND METHODS

Clinical results and resource utilization from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT following carmustine, etoposide, cytarabine, and melphalan (BEAM) HDC for HD and NHL are presented. The trial was performed in six centers in Germany, the United Kingdom, and Belgium. Resource utilization data were used to project costs and Massay Cancer Center (MCC) in the United States incurred the cost of treating the cohort. Costs were projected to the United States, because the economic implications to United States centers are significant, costs of care vary markedly among countries but resource utilization on this trial did not, and a randomized trial is unlikely to be performed in the United States.

RESULTS

Fifty-eight patients with relapsed HD or NHL underwent HDC with BEAM. The PBPCT and ABMT groups had similar short-term survival after BEAM. PBPCT patients had a shorter hospitalization (median, 17 v 23 days; P = .002), neutrophil recovery (11 v 14 days; P = .005), platelet recovery to > or = 20 x 10(9)/L (16 v 23 days; P = .02), and days of platelet transfusions (6 v 10; P < .001). Estimated costs were $8,531 for ABM harvest and $5,760 for PBPC collection, including filgrastim mobilization. The total estimated average cost was $59,314 for each ABMT patient versus $45,792 for each PBPCT patient. Cost savings of $13,521 (23%) were due to shorter hospitalizations with less supportive care.

CONCLUSION

PBPCT is as safe and more effective than ABMT for HD and NHL in the short term. PBPCT represents a significant cost savings due to lower autograft collection costs, shorter hospital stays, and less supportive care. The savings exceed the costs for filgrastim mobilization and PBPC collection. Actual savings will vary depending on local practice patterns, charges, and costs.
Preservation of the bladder in patients with rhabdomyosarcoma.
Authors: Heyn R , Newton W A , Raney R B , Hamoudi A , Bagwell C , Vietti T , Wharam M , Gehan E , Maurer H M
Published: February 2017

PURPOSE

To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not.

PATIENTS AND METHODS

Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks.

RESULTS

All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In 12 of 14 specimens from 15 patients who retained their bladder, no tumor cells were seen at first or second evaluation. In cystectomy specimens, tumor cellularity was markedly reduced and all tumor cells were in varying degrees of cellular maturation. Review of primary tumor specimens showed a greater degree of cellular maturation in patients with retained bladders than in those who underwent cystectomy.

CONCLUSION

Bladder RMS is responsive to chemotherapy and radiotherapy. Twelve of 26 patients showed complete loss of tumor cells after induction therapy. Cystectomy specimens showed diminished tumor cells with varying degrees of cellular maturation. It is hypothesized that these tumors may have shown further maturation and ultimate loss of matured cells with continuing therapy.
MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children.
Authors: Tonini G P , Boni L , Pession A , Rogers D , Iolascon A , Basso G , Cordero di Montezemolo L , Casale F , Pession A , Perri P , Mazzocco K , Scaruffi P , Lo Cunsolo C , Marchese N , Milanaccio C , Conte M , Bruzzi P , De Bernardi B
Published: February 2017

PURPOSE

To evaluate the prognostic role of MYCN oncogene amplification in children with neuroblastoma.

PATIENTS AND METHODS

Of 694 children (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (42%) were evaluated at diagnosis for MYCN gene amplification.

RESULTS

Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified (> or = three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate was higher for children aged less than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This association held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable characteristics, in particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplified MYCN survive. In a multivariate analysis, the prognostic role of MYCN amplification, age, and stage was confirmed, but the size of the effect of MYCN was dependent on age and stage.

CONCLUSION

MYCN amplification is associated with a worse prognosis in children with neuroblastoma at all ages and stages except 4s. This association is most pronounced in children with otherwise favorable prognostic indicators, and in these children should be considered as an indication for more intensive intervention.
Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients.
Authors: Marx C M , Stein J , Tyler M K , Nieder M L , Shurin S B , Blumer J L
Published: February 2017

PURPOSE

To compare the efficacy, characteristics of onset/recovery, and safety of ketamine/atropine/midazolam with meperidine/midazolam used as premedication for painful procedures in children with cancer.

METHODS

A randomized, double-blind crossover trial for two successive painful procedures (bone marrow aspiration or biopsy, lumbar puncture, or combined procedures) was performed at a referral-based pediatric hematology-oncology clinic and associated inpatient service of a university teaching hospital. Twenty-two children, aged 24 to 178 months, were enrolled and 18 (81.8%) completed the double-blind, crossover trial. Each child received intravenous premedication with either meperidine 2 mg/kg and midazolam 0.1 mg/kg (MM) or atropine 0.01 mg/kg, midazolam 0.05 mg/kg, and ketamine 1.5 mg/kg (KM) on one occasion followed by the alternative regimen on a second occasion. The initial premedication regimen was chosen by random assignment.

RESULTS

Efficacy was assessed by a trained observer using the Observational Scale of Behavioral Distress-Revised (OSBD-R). Operator, nurse, parent, and patient opinions of efficacy were recorded on a visual analog scale (VAS). Side effects were monitored by pulse oximetry, nasal end-tidal capnography, and serial blood pressure measurements. Use of KM resulted in significantly less procedural distress than MM (1.37 +/- 2.20 v 7.04 +/- 8.06 OSBD-R units; P < .05). Both operators and nurses rated KM more effective than MM. KM use was associated with earlier readiness for the procedure (19.2 v 24.0 minutes) and more rapid recovery (39.3 v 74.6 minutes for removal of monitoring devices and 58.5 v 87.1 minutes for discharge). Procedures undertaken after ketamine sedation were associated with fewer side effects than observed with MM sedation (hypoxia, 17.7% v 82.4%; hypotension, 16.6% v 55.6%; reduced respiratory rate, 0% v 38.9%). The incidence of emergence reactions or behavioral abnormalities within 24 hours postprocedure was similar in both treatment groups. At 7 days postprocedure, no child had persistent behavioral abnormalities and all children had amnesia for the procedure. Parents and children expressed a preference for KM over MM in 12 of 18 cases (P < .05).

CONCLUSION

A premedication regimen of KM produced superior sedation with a faster onset and recovery and fewer side effects than a MM combination.
Impact of selection process on response rate and long-term survival of potential high-dose chemotherapy candidates treated with standard-dose doxorubicin-containing chemotherapy in patients with metastatic breast cancer.
Authors: Rahman Z U , Frye D K , Buzdar A U , Smith T L , Asmar L , Champlin R E , Hortobagyi G N
Published: February 2017

PURPOSE

Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy.

PATIENTS AND METHODS

Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates.

RESULTS

A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years.

CONCLUSION

This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.
Patient selection in high-dose chemotherapy trials: relevance in high-risk breast cancer.
Authors: García-Carbonero R , Hidalgo M , Paz-Ares L , Calzas J , Gómez H , Guerra J A , Hitt R , Hornedo J , Colomer R , Cortés-Funes H
Published: February 2017

PURPOSE

To evaluate the impact of the selection criteria that are used in current high-dose consolidation chemotherapy (HDCT) trials on the outcome of high-risk breast cancer patients treated with conventional adjuvant chemotherapy.

PATIENTS AND METHODS

From 1975 to 1995, 265 breast cancer patients at our institution showed involvement of ten or more positive axillary lymph nodes. Of these, 171 received standard adjuvant combination chemotherapy, but not HDCT consolidation, and were the subjects of our study. One hundred twenty-eight patients met the standard selection criteria for HDCT with hematological support (< 60 years, no significant concomitant disease, and no progression during adjuvant treatment), whereas 43 did not. Clinical outcome was analyzed by using disease-free survival (DFS) and overall survival (OS) as endpoints. To provide an assessment of the short-term efficacy of HDCT, we also evaluated the outcome in a cohort of 39 patients from the last 4 years who met the criteria for, and were actually treated with, HDCT after adjuvant chemotherapy.

RESULTS

With a median follow-up of 4.4 years (range, 0.7 to 17.2 years), 112 of the 171 patients have had a relapse, and 87 have died. The estimated 5-year DFS was 32.3%, and OS was 49.4%. DFS was significantly higher for patients who met the HDCT criteria (36.6% at 5 years) than for those who did not (15.8% at 5 years; P < .05). OS was also significantly more favorable in patients meeting HDCT criteria (55.4% at 5 years) than in patients not meeting HDCT criteria (22.7% at 5 years; P < .01). We performed a multivariate analysis to adjust for other potential prognostic factors and found that meeting the HDCT criteria and having undergone locoregional radiotherapy were the only significant independent predictors for DFS and OS. Finally, we compared the outcome of the 128 patients who met the HDCT criteria and were treated with conventional adjuvant chemotherapy only with that of the 39 patients who met the criteria and who actually underwent HDCT, and we did not observe significant differences in the DFS or OS between these groups.

CONCLUSIONS

Meeting HDCT inclusion criteria is an independent indicator of favorable prognosis in high-risk breast cancer patients. The selection of patients by these criteria may explain, at least in part, the promising short-term results of nonrandomized adjuvant HDCT trials in high-risk breast cancer.
Prospectively randomized North Central Cancer Treatment Group trial of intensive-course fluorouracil combined with the l-isomer of intravenous leucovorin, oral leucovorin, or intravenous leucovorin for the treatment of advanced colorectal cancer.
Authors: Goldberg R M , Hatfield A K , Kahn M , Sargent D J , Knost J A , O'Connell M J , Krook J E , Maillard J A , Wiesenfeld M , Schaefer P L , Tirona M T , Moertel C G
Published: February 2017

PURPOSE

A three-arm randomized phase III trial in advanced colorectal cancer patients was designed to test whether substitution of an equivalent dose of (1) l-leucovorin or (2) oral leucovorin would more effectively potentiate fluorouracil (5-FU) than standard intravenous (I.V.) (d,l)-leucovorin.

PATIENTS AND METHODS

A total of 926 chemotherapy-naive patients participated. Patients received one of three treatments: (A) intensive-course 5-FU plus l-leucovorin with I.V. leucovorin (Immunex Corp, Seattle, WA) at 100 mg/m2 and I.V. 5-FU at 370 mg/m2; (B) intensive-course 5-FU plus oral (d,l)-leucovorin with oral leucovarin at 125 mg/m2 on hours 0, 1, 2, and 3 (total dose, 500 mg/m2) followed by 5-FU 370 mg/m2 on hour 4; or (C) intensive-course 5-FU plus I.V. (d,l)-leucovorin with I.V. leucovorin 200 mg/m2 and 5-FU 370 mg/m2. Drugs were administered daily for 5 consecutive days. Courses were repeated at 4 and 8 weeks, and every 5 weeks thereafter. Dosage was reduced for neutropenia, thrombocytopenia, diarrhea, stomatitis, and dermatitis.

RESULTS

Of 926 eligible patients, 756 have died. The overall response rate for patients with measurable disease was 32% (165 of 514). There were no differences between regimens in response rates (arm A, 28% [47 of 140]; arm B, 34% [60 of 174]; and arm C, 34% [58 of 170]) or in survival. There have been nine possible chemotherapy-related fatalities. Grade III to IV toxic effects did not differ appreciably by arm and included stomatitis (12% to 14%), diarrhea (15% to 19%), nausea (7% to 9%), and vomiting (6% to 8%).

CONCLUSION

There was no difference in response, survival, or toxicity between these three different leucovorin formulations combined with 5-FU.
Treatment of newly diagnosed acute promyelocytic leukemia without cytarabine.
Authors: Estey E , Thall P F , Pierce S , Kantarjian H , Keating M
Published: February 2017

PURPOSE

To determine the effect of omission of cytarabine (ara-C) from treatment of newly diagnosed acute promyelocytic leukemia (APL), which allows administration of more anthracycline.

PATIENTS AND METHODS

Induction consisted of all-trans retinoic acid (ATRA) 45 mg/m2 daily until complete remission (CR) and idarubicin 12 mg/m2 daily for 4 days beginning on day 5 of ATRA. Patients in CR received two courses of idarubicin 12 mg/m2 daily for 3 days and then, until 2 years post-CR date, alternated three cycles of mercaptopurine, vincristine, methotrexate, and prednisone (POMP) with one cycle of idarubicin 12 mg/m2 daily for 2 days. Results in the 43 patients treated (41 with t(15;17) on standard or Southern analysis) were compared with those in 57 historic newly diagnosed APL patients given ara-C with either doxorubicin, amsacrine (AMSA), or daunorubicin without ATRA, using logistic and Cox regression to assess effects of non-treatment-related covariates on patient outcomes.

RESULTS

The CR rate in the current group was 77% (95% confidence interval [CI], 62% to 88%) and was not significantly different from the historic rate. In contrast, disease-free survival (DFS) in CR is superior in the current group (probability at 1 year 0.87; 95% CI, 0.73 to 1.0). This has translated into superior overall DFS for the current group (P = .03 adjusting for the predictive covariates initial WBC and platelet count; 1-year DFS probability 0.67; 95% CI, 0.52 to 0.82; median follow-up 102 weeks). The current treatment appears better both in patients with and without t(15; 17) on standard cytogenetic analysis.

CONCLUSION

Given the difficulties inherent in comparing sequential studies and recognizing the multiple differences in treatment between current and historic groups, our results suggest that a large randomized trial incorporating use of ATRA should assess the utility of omitting ara-C from treatment of newly diagnosed APL, thus allowing delivery of more anthracycline.
Paclitaxel by 96-hour continuous infusion in combination with cisplatin: a phase I trial in patients with advanced lung cancer.
Authors: Georgiadis M S , Schuler B S , Brown J E , Kieffer L V , Steinberg S M , Wilson W H , Takimoto C H , Kelley M J , Johnson B E
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer.

PATIENTS AND METHODS

Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). Patients received paclitaxel doses of 100 to 180 mg/m2/96 hours and cisplatin doses of 60 to 80 mg/m2 as a single 30-minute bolus injection at the end of the paclitaxel infusion.

RESULTS

Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m2/96 hours and cisplatin 80 mg/m2. With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m2/96 hours and cisplatin 80 mg/m2. Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months.

CONCLUSION

The MTD without G-CSF is paclitaxel 120 mg/m2/96 hours and cisplatin 80 mg/m2, and the MTD with G-CSF is paclitaxel 160 mg/m2/96 hours and cisplatin 80 mg/m2. Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC.
Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte.
Authors: Haioun C , Lepage E , Gisselbrecht C , Bastion Y , Coiffier B , Brice P , Bosly A , Dupriez B , Nouvel C , Tilly H , Lederlin P , Biron P , Brière J , Gaulard P , Reyes F
Published: February 2017

PURPOSE

To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index.

PATIENTS AND METHODS

Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm.

RESULTS

Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49).

CONCLUSION

This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.
Fatty acid composition of adipose tissue, an indication of dietary fatty acids, and breast cancer prognosis.
Authors: Petrek J A , Hudgins L C , Ho M , Bajorunas D R , Hirsch J
Published: February 2017

PURPOSE

Fatty acid composition of adipose tissue is an indicator of the long-term ingestion pattern of several specific fatty acids. There is good correlation of antecedent diet with the essential fatty acids, and there is reflection of the diet with the fatty acids that can be synthesized. The relationship between the fatty acid levels and lymph node status and clinical outcome was examined.

METHODS

At the time of diagnostic surgery, 161 women with clinical stage T1NO breast cancer had subcutaneous adipose tissue (breast and abdominal) aspirated. The concentrations of 35 fatty acids, seven summed classes, and six fatty acid groups were measured by capillary gas chromatography. Lymph node status was determined with axillary dissection, and patients were followed-up (mean, 7.3 years) for clinical outcome.

RESULTS

There was no significant association of any adipose tissue fatty acids with overall survival, although few (16 of 161 women) died of breast cancer. However, the odds of having positive lymph nodes (57 of 161 women) were significantly higher for women with a greater adipose tissue proportion of oleic acid (odds ratio [OR], 7.56; 95% confidence interval [CI], 1.78 to 32.1) or total saturated acids (OR, 8.43; 95% CI, 1.48 to 40.0) and significantly lower with a higher proportion of trans fatty acids (OR, 0.24; 95% CI, 0.07 to 0.77), as assessed by multivariate logistic regression.

CONCLUSION

These data support previous research with dietary questionnaire methodology, suggesting that specific dietary fatty acids may be associated with breast cancer promotion. Further research with long-term clinical follow-up is necessary to investigate these observations in large, diverse populations before dietary recommendations can be envisioned.
Family history of prostate cancer in patients with localized prostate cancer: an independent predictor of treatment outcome.
Authors: Kupelian P A , Kupelian V A , Witte J S , Macklis R , Klein E A
Published: February 2017

PURPOSE

To determine if familial prostate cancer patients have a less favorable prognosis than patients with sporadic prostate cancer after treatment for localized disease with either radiotherapy (RT) or radical prostatectomy (RP).

PATIENTS AND METHODS

One thousand thirty-eight patients treated with either RT (n = 583) or RP (n = 455) were included in this analysis. These patients were noted as having a positive family history if they confirmed the diagnosis of prostate cancer in a first-degree relative. The outcome of interest was biochemical relapse-free survival (bRFS). We used proportional hazards to analyze the effect of the presence of family history and other potential confounding variables (ie, age, treatment modality, stage, biopsy Gleason sum [GS], and initial prostate-specific antigen [iPSA] levels) on treatment outcome.

RESULTS

Eleven percent of all patients had a positive family history. The 5-year bRFS rates for patients with negative and positive family histories were 52% and 29%, respectively (P < .001). The potential confounders with bRFS rates were iPSA levels, biopsy GS, and clinical tumor stage; treatment modality and age did not appear to be associated with outcome. After adjusting for potential confounders, family history of prostate cancer remained strongly associated with biochemical failure.

CONCLUSION

This is the first study to demonstrate that the presence of a family history of prostate cancer correlates with treatment outcome in a large unselected series of patients. Our findings suggest that familial prostate cancer may have a more aggressive course than nonfamilial prostate cancer, and that clinical and/or pathologic parameters may not adequately predict this course.
Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.
Authors: Steffens M G , Boerman O C , Oosterwijk-Wakka J C , Oosterhof G O , Witjes J A , Koenders E B , Oyen W J , Buijs W C , Debruyne F M , Corstens F H , Oosterwijk E
Published: February 2017

PURPOSE

Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody.

PATIENTS AND METHODS

Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed.

RESULTS

In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients.

CONCLUSION

131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.
Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.
Authors: Wendum D , Sebban C , Gaulard P , Coiffier B , Tilly H , Cazals D , Boehn A , Casasnovas R O , Bouabdallah R , Jaubert J , Ferrant A , Diebold J , de Mascarel A , Gisselbrecht C
Published: February 2017

PURPOSE

The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial.

PATIENTS AND METHODS

Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol.

RESULTS

After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%).

CONCLUSION

FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.
Phase I and pharmacologic study of penclomedine, a novel alkylating agent, in patients with solid tumors.
Authors: O'Reilly S , Grochow L B , Donehower R C , Chen T L , Bowling K , Hartman N R , Struck R F , Rowinsky E K
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD), principal toxicities, and pharmacologic behavior of penclomedine, a novel alkylating agent.

PATIENTS AND METHODS

Penclomedine (45 to 550 mg/ m2/d every 3 weeks) was administered as a 1- or 3-hour intravenous (IV) infusion for 5 consecutive days to patients with solid tumors.

RESULTS

On a 1-hour dosing schedule, ataxia, vertigo, nystagmus, and a motor aphasia were the principal toxicities of penclomedine. These neurologic effects were dose-related, and evolved from complaints of somnolence and dizziness, to more pronounced signs and symptoms of cerebellar dysfunction. Up to and including doses of 415 mg/m2, these effects were well tolerated and resolved within 2 hours posttreatment. In contrast, both patients treated at the 550-mg/m2 dose level experienced a dose-limiting constellation of perinfusional aphasia and vertigo, with either ataxia of over 2 weeks' duration or recurrent dizziness. Prolongation of the infusion duration to 3 hours at this dose level resulted in less neurotoxicity; however, delayed trilineage hematologic toxicity precluded timely administration on this schedule. A statistically significant relationship was demonstrated between the development of ataxia and maximum plasma concentrations of penclomedine.

CONCLUSION

Neurotoxicity was the dose-limiting toxicity (DLT) of penclomedine administered as a 1-hour infusion daily for 5 days every 3 weeks, and the recommended dose for further evaluations was 415 mg/m2. The nature of the principal toxicities and the lack of any detectible antitumor activity indicate that phase II evaluations of penclomedine on this administration schedule should be focused on specific disease settings, such as breast cancer and intracerebral tumors, in which antitumor activity has been demonstrated.
Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.
Authors: Schwartsmann G , Sprinz E , Kromfield M , Kalakun L , Sander E , Prolla G , Di Leone L , Gerhardt L , Mans D R
Published: February 2017

PURPOSE

In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy.

PATIENTS AND METHODS

Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard.

RESULTS

The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing.

CONCLUSION

At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.
Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia: a matched-pair analysis. Berlin-Frankfurt-Münster Study Group.
Authors: Beyermann B , Adams H P , Henze G
Published: February 2017

PURPOSE

The translocation t(9;22)(q34;q11), known as Philadelphia chromosome (Ph1) or its molecular equivalent the expression of BCR-ABL-mRNA, is one of the most striking and well-characterized cytogenetic abnormalities in leukemia. Although investigated for more than 30 years, it remains unclear whether the Ph1 is an independent risk factor for outcome of leukemia or not.

METHODS

A matched-pair analysis was performed within a homogeneous group of patients, which consisted of children who presented with a first relapse of acute lymphoblastic leukemia (ALL) who were treated according to ALL relapse trials (ALL-REZ BFM) protocols. A total of 307 patients were eligible for this analysis: 30 positive and 277 negative for Ph1. Positive patients were matched exactly for time point of relapse (on [during] or off [after cessation of] front-line therapy), site, and immunophenotype, and as close as possible for duration of first remission, peripheral blast-cell count, WBC count, and year of relapse diagnosis.

RESULTS

The probability of event-free survival is 0.46 at 5 years for negative and 0.11 for positive patients, respectively (P = .0006). Multivariate analysis showed risk ratios of 4.229 for relapse on therapy, 3.561 for Ph1 and/or expression of BCR-ABL- mRNA, 1.691 for high peripheral blast-cell count, and 0.232 for bone marrow transplantation.

CONCLUSION

It was shown that the Ph1 is indeed an independent risk factor in childhood relapsed ALL. There are striking similarities between these patients and children at initial diagnosis, as well as adult patients. Therefore, it is highly suggestive that the Ph1 is also an independent risk factor under all of these circumstances.
Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on projections from Eastern Cooperative Oncology Group 1684.
Authors: Hillner B E , Kirkwood J M , Atkins M B , Johnson E R , Smith T J
Published: February 2017

PURPOSE

Interferon alfa-2b (IFN) in a randomized clinical trial (E1684) prolonged relapse-free and total survival in high-risk resected melanoma. However, the costs and toxicities of IFN are barriers to its widespread use. This study was undertaken to analyze the projected costs and long-term benefits of IFN by combining prospectively collected data on IFN actual dosage, time of recurrence, and survival with secondary data on long-term melanoma recurrence risks to project the cost-effectiveness of adjuvant IFN compared with observation.

PATIENTS AND METHODS

Two hypothetical cohorts of 50-year-old melanoma patients whose mean IFN dosage and clinical results were directly taken from E1684 were included in the study. Melanoma recurrence risks beyond 5 years were derived from international databases. Melanoma recurrence care costs and quality-of-life adjustments, when considered, were based on expert consensus. End points were incremental costs, life-years gained, and cost per life-year gained with and without quality-of-life adjustments.

RESULTS

The IFN cohort was projected to have an increased (undiscounted) survival of 0.52 years at 7 years and 1.90 years over a lifetime. The projected incremental cost (in 1996 United States dollars) per life-year gained in the IFN cohort ranged from $13,700 after 35 years to $32,600 at 7 years, the median follow-up of E1684. Using assigned quality-of-life values for IFN and recurrence, the lifetime cost per quality adjusted life-year increased to $15,200. Even if treatment costs for recurrence were excluded, the lifetime incremental cost per life-year gained was $21,600.

CONCLUSION

The cost and toxicity of IFN must be balanced against its projected benefits in high-risk melanoma. The derived cost-effectiveness and cost-utility ratios for IFN were comparable to other cancer interventions for which cost-effectiveness analysis has been performed.
Treatment of Kaposi's sarcoma after solid organ transplantation.
Authors: Shepherd F A , Maher E , Cardella C , Cole E , Greig P , Wade J A , Levy G
Published: February 2017

PURPOSE

This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting.

MATERIALS AND METHODS

The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks.

RESULTS

Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity.

CONCLUSION

KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.
Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study.
Authors: Whitehead R P , Jacobson J , Brown T D , Taylor S A , Weiss G R , Macdonald J S
Published: February 2017

PURPOSE

Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer.

PATIENTS AND METHODS

All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts.

RESULTS

Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis.

CONCLUSION

Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.