bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.
Authors: Osoba D , Zee B , Pater J , Warr D , Latreille J , Kaizer L
Published: February 2017

PURPOSE

To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables.

PATIENTS AND METHODS

Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV.

RESULTS

Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors.

CONCLUSION

Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.
IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.
Authors: Maloney D G , Grillo-López A J , Bodkin D J , White C A , Liles T M , Royston I , Varns C , Rosenberg J , Levy R
Published: February 2017

PURPOSE

To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma.

PATIENTS AND METHODS

Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8.

RESULTS

Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR.

CONCLUSION

IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.
Role of the retinoblastoma protein in the pathogenesis of human cancer.
Authors: Sellers W R , Kaelin W G
Published: February 2017

The retinoblastoma gene (RB-1) was originally identified as the gene involved in hereditary retinoblastoma. However, RB-1 mutations are found in a number of common mesenchymal and epithelial malignancies. The retinoblastoma protein (pRB) acts as a transcriptional regulator of genes involved in DNA synthesis and cell-cycle control. In this regard, the functional interaction between pRB and the E2F transcription factor family appears to be critical. The pRB-E2F interaction is, in turn, regulated by a pathway that includes cyclin D1, cdk4, and p16. Mutations that affect this pathway have been documented in nearly every type of adult cancer. Thus, perturbation of pRB function may be required for the development of cancer. Insights into the biochemical functions of pRB, and its upstream regulators, may form the basis for the development of novel antineoplastic agents.
Successful pregnancy after allogeneic bone marrow transplant with embryos isolated before transplant.
Authors: Lipton J H , Virro M , Solow H
Published: February 2017

METHODS AND RESULTS: Autologous embryos from in vitro-fertilized ova were successfully implanted in a 29-year-old woman, 2 years after successful allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML). A second pregnancy, similarly initiated, is in progress at 4 years posttransplant. CONCLUSION: Our experience offers a fertility-salvaging technique to some women after cytotoxic therapy, where time permits ovarian hyperstimulation before the need for definitive myeloblative therapy of their malignancy, and where the risk of subsequent infertility is high.
Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies.
Authors: Ippoliti C , Champlin R , Bugazia N , Przepiorka D , Neumann J , Giralt S , Khouri I , Gajewski J
Published: February 2017

PURPOSE

Diarrhea associated with acute gastrointestinal (GI) graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) can result in severe morbidity and mortality. A pilot study was conducted to evaluate the efficacy and toxicity of octreotide in the management of diarrhea in patients with GVHD after allogeneic BMT.

PATIENTS AND METHODS

Twenty-one patients entered the study. Patients received either peripheral-blood stem cells (n = 13) or bone marrow (n = 8). Seven patients had grade 4, 13 grade 3, and one grade 2 GVHD. Intravenous (I.V.) octreotide 500 microg every 8 hours for 7 days was administered. Octreotide treatment was discontinued if no response was observed after 7 days or for grade 4 toxicity.

RESULTS

Fifteen (71%) of 21 treated patients had a complete response within 7 days of the initiation of octreotide; three (14%) had a partial response and three (14%) failed to respond to treatment. Toxicities were minimal; hyperglycemia was seen in four patients and one patient developed a partial ileus. Octreotide was discontinued and the ileus resolved within 48 hours.

CONCLUSION

If initiated early in the course of GI GVHD, octreotide appears to be an effective, well-tolerated agent in reducing severe voluminous diarrhea. Octreotide should be discontinued within 24 hours after the resolution of diarrhea to avoid the development of ileus. Because no additional reduction in the volume of diarrhea occurred after 7 days of therapy, continuation of the drug beyond this time is not cost effective.
Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities.
Authors: Hainsworth J D , Gray J R , Stroup S L , Kalman L A , Patten J E , Hopkins L G , Thomas M , Greco F A
Published: February 2017

PURPOSE

In two sequential phase II studies, we evaluate the feasibility and efficacy of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of small-cell lung cancer.

PATIENTS AND METHODS

One hundred seventeen patients with small-cell lung cancer were treated between June 1993 and July 1996. The first 38 patients received a lower-dose regimen: paclitaxel 135 mg/m2 by 1-hour infusion, carboplatin at an area under the concentration-time curve (AUC) of 5.0, and etoposide 50 mg alternating with 100 mg orally on days 1 to 10. When only mild myelosuppression was observed, doses of paclitaxel and carboplatin were increased in the subsequent 79 patients (paclitaxel 200 mg/m2 by 1-hour infusion and carboplatin at an AUC of 6.0). All patients received four courses of treatment, administered at 21-day intervals. Patients with limited-stage small-cell lung cancer also received thoracic radiation therapy (1.8 Gy/d; total dose, 45 Gy) administered concurrently with courses 3 and 4 of chemotherapy.

RESULTS

Seventy-two of 79 patients (91%) who receive the higher-dose regimen had major responses. Thirty-two of 38 (84%) with extensive-stage disease responded (21% complete response rate); median survival was 10 months for this group. With limited-stage disease, the overall response rate was 98%, with 71% complete responses; the median survival time has not been reached at 16 months. Median survival in extensive-stage patients was longer in patients who received the higher-dose regimen (10 months) than in the previous group treated with lower doses (7 months; P = .008). The higher-dose regimen was well tolerated, with myelosuppression being the major toxicity. Compared with the lower-dose regimen, grade 3/4 neutropenia increased from 8% to 38% of courses, but the incidence of hospitalization for neutropenia and fever did not increase. Other nonhematologic toxicities were uncommon, and did not increase substantially with the higher-dose regimen.

CONCLUSION

Paclitaxel can be added at full dose (200 mg/m2) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Median survival times in both extensive- and limited-stage patients compare favorably with other reported regimens. This regimen merits further investigation, and a randomized trial to compare this regimen with a standard carboplatin/etoposide combination is underway.
Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.
Authors: Warzocha K , Salles G , Bienvenu J , Bastion Y , Dumontet C , Renard N , Neidhardt-Berard E M , Coiffier B
Published: February 2017

PURPOSE

A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas.

PATIENTS AND METHODS

One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA).

RESULTS

Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI.

CONCLUSION

TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.
Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma.
Authors: Watts M J , Sullivan A M , Jamieson E , Pearce R , Fielding A , Devereux S , Goldstone A H , Linch D C
Published: February 2017

PURPOSE

To define parameters that predict for rapid engraftment after peripheral-blood stem-cell (PBSC) transplantation, progenitor thresholds, the proportion of patients who achieve these thresholds with a standardized mobilization regimen, and the factors that predict for mobilization efficiency.

PATIENTS AND METHODS

One hundred and one patients with pretreated lymphoma were mobilized with cyclophosphamide 1.5 g/m2 and granulocyte colony-stimulating factor (G-CSF), with the first apheresis performed when the recovery WBC count was > or = 5.0 x 10(9)/L. The relationship between the number of progenitor cells collected and patient age, sex, diagnosis, prior radiotherapy, and time since last chemotherapy was determined by multivariate analysis. The relationship between these factors, progenitor numbers returned, post-PBSC G-CSF, and hematologic recovery was performed in 81 patients following chemotherapy with carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM protocol).

RESULTS

No BEAM recipients had delayed neutrophil recovery beyond 28 days. Delayed platelet recovery occurred in 7.4% and minimum and optimum thresholds of 1 x 10(6) and 3.5 x 10(6) CD34+ cells/kg and 1 x 10(5) and 3.5 x 10(5) granulocyte-macrophage colony-forming cells (GM-CFC)/kg were established. Hematologic recovery was adversely affected by prior treatment with mini-BEAM, and neutrophil recovery was accelerated by post-PBSC G-CSF. The minimum GM-CFC threshold was achieved with a single apheresis in 83% of patients and in 90% with two aphereses. The optimal threshold was achieved with two leukaphereses in 69% of patients. Prior radiotherapy adversely affected mobilization.

CONCLUSION

Hematopoietic recovery following PBSC is dependent on progenitor-cell number infused and affect of previous chemotherapy on progenitor quality. Progenitor-cell mobilization is adversely affected by prior radiotherapy. The minimum threshold of GM-CFC required is achieved in most patients with a single apheresis, but an optimal collection usually requires at least two harvests.
Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a cooperative Children's Cancer Group and National Institutes of Health study.
Authors: Zeltzer L K , Chen E , Weiss R , Guo M D , Robison L L , Meadows A T , Mills J L , Nicholson H S , Byrne J
Published: February 2017

PURPOSE

To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood.

PATIENTS AND METHODS

Adult survivors (n = 580), aged > or = 18 years, who were treated before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state.

RESULTS

Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P<.01) and reported more tension (P< .01), depression (P<.01), anger (P<.01), and confusion (P<.01), but not more fatigue or less vigor. Female, minority, and unemployed survivors reported the highest total mood disturbance. Overall, survivors were more likely to be unemployed (P<.05) or working less than half-time (P<.01) compared with controls.

CONCLUSION

This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention.
Unrelated donor bone marrow transplantation for children with acute leukemia.
Authors: Davies S M , Wagner J E , Shu X O , Blazar B R , Katsanis E , Orchard P J , Kersey J H , Dusenbery K E , Weisdorf D J , McGlave P B , Ramsay N K
Published: February 2017

PURPOSE

To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias.

PATIENTS AND METHODS

Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus.

RESULTS

The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years.

CONCLUSION

URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.
Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.
Authors: Lacava J A , Leone B A , Machiavelli M , Romero A O , Perez J E , Elem Y L , Ferreyra R , Focaccia G , Suttora G , Salvadori M A , Cuevas M A , Acuña L R , Acuña J R , Langhi M , Amato S , Castaldi J , Arroyo A , Vallejo C T
Published: February 2017

PURPOSE

To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC).

PATIENTS AND METHODS

Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team.

RESULTS

One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected.

CONCLUSION

VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.
Association of local recurrence with subsequent survival in extremity soft tissue sarcoma.
Authors: Lewis J J , Leung D , Heslin M , Woodruff J M , Brennan M F
Published: February 2017

PURPOSE

The aim of this study was to analyze local recurrence in a large cohort of prospectively followed patients with primary extremity soft tissue sarcoma. In particular, we analyzed the correlation of local recurrence with subsequent metastasis and disease-specific survival.

PATIENTS AND METHODS

Patients who underwent treatment for primary extremity soft tissue sarcoma from July 1982 through July 1995 at Memorial Sloan-Kettering Cancer Center were the subject of this study. Local recurrence, distant metastasis, and disease-specific survival were used as end points of the study. The influence of local recurrence on subsequent distant metastasis and disease-specific survival were examined using the Cox proportional hazards model.

RESULTS

We treated 911 patients, of whom 297 (33%) developed recurrent disease. Local recurrence occurred in 116 patients (13%), metastasis in 167 (18%), and synchronous local recurrence and metastasis in 13 (2%). Of 116 patients who developed local recurrence, 38 subsequently developed metastasis and 34 died of disease. Metastasis after local recurrence was predicted in patients with initial high-grade (P = .005; risk = 3.5) or deep (P = .02; risk = 2.9) tumors. Tumor mortality after local recurrence was predicted in patients with initial high-grade (P = .007; risk = 3.7) or large (> 5 cm; P = .01; risk = 3.2) primary tumors.

DISCUSSION

These findings suggest that there is a strong association of local recurrence with the development of subsequent metastasis and tumor mortality, and that local recurrence is a poor prognostic factor. It would seem prudent to consider patients who develop local recurrence and have high-grade tumors as being at high risk for systemic disease and therefore eligible for investigational adjuvant systemic therapy.
Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy.
Authors: Northfelt D W , Dezube B J , Thommes J A , Levine R , Von Roenn J H , Dosik G M , Rios A , Krown S E , DuMond C , Mamelok R D
Published: February 2017

PURPOSE

To determine the efficacy and safety of pegylated-liposomal doxorubicin in patients with AIDS and Kaposi's sarcoma (AIDS-KS) who experienced failure of standard chemotherapy.

METHODS

Fifty-three patients with advanced AIDS-KS who experienced disease progression or intolerable toxicities while receiving standard doxorubicin/bleomycin/vincristine (ABV) or bleomycin/vincristine (BV) chemotherapy were identified from a cohort of patients who were then treated with pegylated-liposomal doxorubicin. Patients received 20 mg/m2 pegylated-liposomal doxorubicin (Doxil; Sequus Pharmaceuticals, Inc, Menlo Park, CA) every 3 weeks.

RESULTS

Nineteen patients (36%) had a partial response (PR) and one patient had a clinical complete response (CCR). The median duration of response and time (from study entry) to treatment failure were 128 and 134 days, respectively. Of 28 patients who experienced disease progression while receiving combination regimens that contained standard doxorubicin, the PR rate was 32%, which suggests that the pegylated-liposomal encapsulation increases the therapeutic effect of doxorubicin. Patients obtained clinical benefits such as flattening of lesions (48%), improved lesion color (56%), relief of pain (45%), and loss of edema (83%). Forty-nine percent of patients had more than one clinical benefit. The most common adverse effect was leukopenia, which occurred in 40% of patients. Only 15% of patients had nausea and/or vomiting, none of which was severe; 9% experienced alopecia, also generally mild.

CONCLUSION

Pegylated-liposomal doxorubicin offers a new alternative for treatment of patients who have experienced failure of standard chemotherapy for AIDS-KS.
Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor.
Authors: Demirer T , Buckner C D , Storer B , Lilleby K , Rowley S , Clift R , Appelbaum F R , Storb R , Bensinger W I
Published: February 2017

PURPOSE

To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF).

PATIENTS AND METHODS

One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells.

RESULTS

The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield.

CONCLUSION

Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.
Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.
Authors: Choi N C , Carey R W , Daly W , Mathisen D , Wain J , Wright C , Lynch T , Grossbard M , Grillo H
Published: February 2017

PURPOSE

The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival.

METHODS

Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score > or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation.

RESULTS

Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade > or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04).

CONCLUSION

Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.
Randomized placebo-controlled clinical trial of high-dose interleukin-2 in combination with a soluble p75 tumor necrosis factor receptor immunoglobulin G chimera in patients with advanced melanoma and renal cell carcinoma.
Authors: Du Bois J S , Trehu E G , Mier J W , Shapiro L , Epstein M , Klempner M , Dinarello C , Kappler K , Ronayne L , Rand W , Atkins M B
Published: February 2017

PURPOSE

A randomized, double-blind, placebo-controlled trial was performed to compare the toxicity and biologic effects of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus the recombinant human soluble p75 tumor necrosis factor (TNF) receptor immunoglobulin G (IgG) chimera (rhuTNFR:Fc) with high-dose IL-2 alone in patients with advanced melanoma and renal cell carcinoma.

PATIENTS AND METHODS

Twenty patients with advanced melanoma or renal cell carcinoma were randomized to receive IL-2 (Chiron, Emeryville, CA) 600,000 IU/kg every 8 hours on days 1 to 5 and 15 to 19 (maximum, 28 doses) combined with placebo or the rhuTNFR:Fc fusion protein (Immunex, Seattle, WA) 10 mg/m2 on days 1 and 15 and 5 mg/m2 on days 3, 5, 17, and 19. The impact of rhuTNFR:Fc on IL-2 toxicity and biologic effects was evaluated.

RESULTS

No clinically significant difference in toxicity was observed in the two treatment arms. The adjusted median number of IL-2 doses administered during cycle 1 was 24.5 (range, seven to 28) and 21.5 (range, five to 27) for the placebo and rhuTNFR:Fc arms, respectively (P = .544). IL-2-induced TNF bioactivity, neutrophil chemotactic defect, and serum IL-6, IL-8, and IL-1 receptor antagonist (IL-1RA) induction were suppressed by rhuTNFR:Fc. Two of nine assessable patients (22%) on IL-2/placebo and three of 10 patients (30%) on IL-2/rhuTNFR:Fc responded.

CONCLUSION

Despite evidence of in vitro neutralization of TNF functional activity and partial inhibition of other secondary biologic effects of IL-2, rhuTNFR:Fc does not reduce the clinical toxicity associated with high-dose IL-2 therapy. These results suggest that the toxicity and antitumor effects of IL-2 treatment are independent of circulating TNF.
Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.
Authors: Mitchell P L , Morland B , Stevens M C , Dick G , Easlea D , Meyer L C , Pinkerton C R
Published: February 2017

PURPOSE

Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective.

PATIENTS AND METHODS

In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated.

RESULTS

Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04).

CONCLUSION

Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.
Timing and magnitude of decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children's Cancer Group.
Authors: Van Tornout J M , Buckley J D , Quinn J J , Feusner J H , Krailo M D , King D R , Hammond G D , Ortega J A
Published: February 2017

PURPOSE

We analyzed data on 31 children with primary unresectable or metastatic hepatoblastoma (HB) to investigate possible prognostic correlations between the serum level of alpha-fetoprotein (AFP), its changes during treatment, and outcome.

PATIENTS AND METHODS

Patients were treated according to the Children's Cancer Group (CCG) protocol 823F, which included an initial surgery before eight courses of chemotherapy that consisted of cisplatin immediately followed by a continuous infusion of doxorubicin. Four courses were given before and four after the second surgery. AFP levels were measured before treatment, before and after second surgery, and at the end of treatment.

RESULTS

Twenty-four of 31 patients showed a decline of > or = 1 log in AFP levels before second surgery (early responders). By the end of treatment, there were 16 patients, all early responders, without clinical or radiographic evidence of tumor and with normal AFP levels. Fifteen of those 16 had a decline of > or = 2 logs in AFP before second surgery (large early response). Of the 15 patients who failed to respond to treatment, 10 died, among whom only one patient had a large early response. A large early response was the strongest independent predictor of outcome in a univariate and multivariate Cox regression model, and patients with such a response had the best survival (P < .0001).

CONCLUSION

For children with unresectable or metastatic HB, early changes in AFP levels are a reliable predictor of outcome and can be used for identification of poor responders to treatment, ie, patients whose AFP level fails to decrease 2 logs before second surgery should be considered for alternative treatment.
Value of caregiver ratings in evaluating the quality of life of patients with cancer.
Authors: Sneeuw K C , Aaronson N K , Sprangers M A , Detmar S B , Wever L D , Schornagel J H
Published: February 2017

PURPOSE

To evaluate the usefulness of caregiver ratings of cancer patients' quality of life (QL), we examined the following: (1) the comparability of responses to a brief standardized QL questionnaire provided by patients, physicians, and informal caregivers; and (2) the relative validity of these ratings.

METHODS

The study sample included cancer patients receiving chemotherapy, their treating physicians, and significant others involved closely in the (informal) care of the patients. During an early phase of treatment and 3 months later, patients and caregivers completed independently the COOP/WONCA charts, covering seven QL domains. At baseline, all sources of information were available for 295 of 320 participating patients (92%). Complete follow-up data were obtained for 189 patient-caregiver triads.

RESULTS

Comparison of mean scores on the COOP/WONCA charts revealed close agreement between patient and caregiver ratings. At the individual patient level, exact or global agreement was observed in the majority of cases (73% to 91%). Corrected for chance agreement, moderate intraclass correlations (ICC) were noted (0.32 to 0.72). Patient, physician, and informal caregiver COOP/WONCA scores were all responsive to changes over time in specific QL domains, but differed in their relative performance. Relative to the patients, the physicians were more efficient in detecting changes over time in physical fitness and overall health, but less so in relation to social function and pain.

CONCLUSION

For studies among patient populations at risk of deteriorating self-report capabilities, physicians and informal caregivers can be useful as alternative or complementary sources of information on cancer patients' QL.
Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer.
Authors: Hayman J A , Fairclough D L , Harris J R , Weeks J C
Published: February 2017

PURPOSE

To assess patients' preferences regarding the trade-off between risks and benefits of radiation therapy after conservative surgery for early-stage breast cancer.

PATIENTS AND METHODS

Utilities (measures of preference) of 97 early-stage breast cancer patients treated with conservative surgery and radiation therapy and 20 medical oncology nurses were assessed for five health states using standard gambles.

RESULTS

Patients had the highest mean utility for treatment with conservative surgery and radiation therapy without a local recurrence (0.92), intermediate utilities for treatment with conservative surgery alone followed either by no local recurrence or by a local recurrence salvaged by conservative surgery and radiation therapy (0.88 and 0.87, respectively), and the lowest utilities for treatment with or without radiation therapy followed by a local recurrence salvaged by mastectomy and reconstructive surgery (0.82 and 0.81, respectively). All differences between health states' utilities were significant (P < .0001), except between the two intermediate and two lowest rated health states. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' utilities or their differences. Nurses' utilities were similar to those of the patients.

CONCLUSIONS

These results strongly suggest that fear of a local recurrence and an actual local recurrence leading to mastectomy have such a negative impact on quality of life that patients are willing to accept the risks and inconvenience of radiation therapy to avoid them. There is also considerable interpatient variability that was not explained by the clinical or sociodemographic factors examined.
Does a centralized radiotherapy system provide adequate access to care?
Authors: Mackillop W J , Groome P A , Zhang-Solomons J , Zhou Y , Feldman-Stewart D , Paszat L , Dixon P , Holowaty E J , Cummings B J
Published: February 2017

PURPOSE

In the Canadian province of Ontario, all radiotherapy is provided by a centrally managed provincial network of nine cancer centers. The primary goal of this study was to determine whether this highly centralized radiotherapy system provides adequate and equitable access to care for the province's dispersed population.

METHODS

The Ontario Cancer Registry (OCR) was used to identify 295,386 cases of invasive cancer, excluding nonmelanoma skin cancer, which were diagnosed in Ontario between 1984 and 1991. Electronic radiotherapy records from each of the province's radiotherapy centers were linked to the registry at the level of the individual case.

RESULTS

The proportion of incident cases treated with radiotherapy was 18.8% at 4 months after diagnosis, 23.7% at 1 year, 25.8% at 2 years, 28.2% at 5 years, and 29.1% at 8 years. These rates of radiotherapy use are much lower than the accepted national and international targets, and lower than rates reported from other jurisdictions. The rate of radiotherapy use at 1 year varied significantly from county to county across Ontario (range, 18.6% to 32.4%; P < 10(-6)), and the highest rates were recorded in communities close to radiotherapy centers. There was a common geographic pattern of rate variations among several disease groups, including breast cancer, lung cancer, the genitourinary malignancies, and the gastrointestinal malignancies.

CONCLUSION

The low and uneven rates of radiotherapy use across the province indicate that Ontario's centralized radiotherapy system does not, at present, provide adequate or equitable access to care.
Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study.
Authors: Delmas P D , Balena R , Confravreux E , Hardouin C , Hardy P , Bremond A
Published: February 2017

PURPOSE

To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis.

PATIENTS AND METHODS

Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment.

RESULTS

Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities.

CONCLUSION

Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.
Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy.
Authors: Swain S M , Whaley F S , Gerber M C , Ewer M S , Bianchine J R , Gams R A
Published: February 2017

PURPOSE

To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m2 confers cardioprotection in patients with advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC).

PATIENTS AND METHODS

In two multicenter studies (088001 and 088006), patients were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a protocol amendment, all patients received open-label DZR after they had reached a cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients randomized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to the PLA arms after the amendment who received FAC and PLA for six courses followed by open-label DZR (PLA/DZR group).

RESULTS

The hazards ratio of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR was 13.1 (95% CI, 3.7 to 46.0; P < .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF. The overall incidence of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA group (P < .001, Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15 courses of therapy, compared with 5% of patients in the PLA group. These results do not appear to be attributable to a time trend.

CONCLUSION

DZR is a highly effective cardioprotective agent when used in patients with advanced breast cancer who continue to receive doxorubicin-based chemotherapy after a cumulative doxorubicin dose of 300 mg/m2 has been reached.
Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.
Authors: Saarto T , Blomqvist C , Välimäki M , Mäkelä P , Sarna S , Elomaa I
Published: February 2017

PURPOSE

In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases.

MATERIALS AND METHODS

Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years.

RESULTS

Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD.

CONCLUSION

Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.