bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypercholesterolemia after chemotherapy for testis cancer.
Authors: Raghavan D , Cox K , Childs A , Grygiel J , Sullivan D
Published: February 2017

PURPOSE

The study was designed to determine prospectively the prevalence of fasting serum lipid abnormalities in patients who were treated with cisplatin-based chemotherapy for germ cell tumors. We unexpectedly had demonstrated hypercholesterolemia in 20 of 30 nonfasting patients in a prior study of long-term toxicity of chemotherapy for germ cell tumors. The present study was designed to explore this phenomenon further.

PATIENTS AND METHODS

Seventeen unselected patients with biopsy-proven germ cell tumors, who underwent cisplatin-based chemotherapy and who had no prior history of cardiac disease nor known hypercholesterolemia, were studied. In addition to the standard staging tests, blood was drawn for a pretreatment fasting lipid screen, which included cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1, B, and (a). Repeat samples were drawn 24 hours after the administration of cisplatin and at intervals of 6 to 24 months after the completion of treatment.

RESULTS

Seven of 17 patients (41%) had higher than desirable levels of total serum cholesterol and low-density lipoprotein cholesterol. Two of them had normal levels before treatment, four had preexisting hypercholesterolemia that increased further, and one patient had an elevated pretreatment level that did not alter. Absolute increases in serum cholesterol were noted in 14 of 17 patients. No consistent patterns of change beyond the reference ranges were found for other serum lipids.

CONCLUSIONS

We have confirmed our initial observation that serum cholesterol increases in patients who received cisplatin-containing chemotherapy regimens for germ cell tumors. Further studies will be necessary to define whether other lipid abnormalities occur and the biologic significance of these findings.
Sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following standard-dose combination chemotherapy with etoposide, ifosfamide, and cisplatin.
Authors: Brugger W , Frisch J , Schulz G , Pressler K , Mertelsmann R , Kanz L
Published: February 2017

PURPOSE

To combine the benefits of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery and recombinant human interleukin-3 (rhIL-3) on platelet recovery, we applied standard-dose chemotherapy with the combined administration of IL-3 and GM-CSF to investigate their efficacy and toxicity.

PATIENTS AND METHODS

Thirty-six patients with advanced malignancies were treated with etoposide (VP16) 500 mg/m2, ifosfamide 4 g/m2, and cisplatin 50 mg/m2 (VIP), followed by the sequential administration of IL-3 (days 1 to 5 subcutaneously [SC]) and GM-CSF (day 6 to 15 SC). Control patients received GM-CSF alone or were treated without hematopoietic growth factors.

RESULTS

Subcutaneous IL-3 and GM-CSF treatment was well tolerated; low-grade fever (World Health Organization grade 1 to 2) was the only consistent clinical symptom. Neutrophil recovery documented that the duration of neutropenia less than 0.1 x 10(9)/L or less than 0.5 x 10(9)/L was identical in GM-CSF as well as IL-3 and GM-CSF-treated patients, but was shortened significantly when compared with patients who were treated without cytokines. Overall platelet recovery was not different significantly in the three treatment groups. The biologic activity of IL-3 in this cytokine combination was reflected in a variety of effects, which included an increase in basophil and eosinophil counts and the induction of circulating hematopoietic progenitor cells.

CONCLUSION

We conclude that after conventional-dose VIP chemotherapy, a shortened treatment course of IL-3 (5 days) sequentially followed by GM-CSF (10 days) combines the benefits of prolonged single GM-CSF treatment on WBC count recovery in all patients and an accelerated platelet recovery only in some intensively pretreated patients.
Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?
Authors: Grilli R , Oxman A D , Julian J A
Published: February 2017

PURPOSE

To estimate the impact of chemotherapy on survival of patients with advanced non-small-cell lung cancer (NSCLC).

METHODS

Randomized controlled trials (RCTs) published in the English-language medical literature between 1970 and 1991 were identified through MEDLINE and the reference lists of relevant articles. Six RCTs that accounted for 635 patients and compared first-line chemotherapy with supportive care in advanced NSCLC and reported survival up to at least 1 year were identified. Cumulative proportions of survival at 3, 6, 9, and 12 months for chemotherapy and control groups were derived from survival curves.

RESULTS

Within each study, the effect of chemotherapy was estimated with a pooled relative risk (RR) across the four 3-month periods. An overall estimate of the RR of death at 1 year (RRM-H) was then calculated and a survival curve for chemotherapy-treated patients was constructed applying the pooled estimate of the RR (RRW) for each 3-month period. Overall, chemotherapy was associated with a 24% (95% confidence interval [CI], 13% to 34%) reduction in the probability of death when compared with supportive care. However, the effect of treatment appeared to decrease significantly after the first 6 months from therapy inception and the mean potential gain in survival, as compared with supportive care, was approximately 6 weeks (95% CI, 1 to 10).

CONCLUSION

Chemotherapy is effective in the treatment of advanced NSCLC, but its impact on the length of survival is limited. Future RCTs should still include an untreated control group and should measure quality of life in addition to survival.
Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.
Authors: Ahlgren J D , Ellison N M , Gottlieb R J , Laluna F , Lokich J J , Sinclair P R , Ueno W , Wampler G L , Yeung K Y , Alt D
Published: February 2017

PURPOSE

To evaluate the efficacy of three hormonal manipulations in the palliation of chemoresistant ovarian cancer, and to analyze the results in the light of other clinical trials.

PATIENTS AND METHODS

Three sequential phase II trials were performed in patients with refractory epithelial ovarian carcinoma, using high-dose megestrol acetate (800 mg/d for 30 days, then 400 mg/d), high-dose tamoxifen (80 mg/d for 30 days, then 40 mg/d), and aminoglutethimide (1 g/d plus tapering doses of hydrocortisone). Results were compared with those described in the world literature from trials of the same or similar agents.

RESULTS

No responses were seen among 30 assessable patients treated with megestrol acetate, and most (but not all) similar trials have reported low response rates. Five responses (17%) were seen among 29 patients treated with tamoxifen. Two responses exceeded 5 years in duration. No responses were seen among 15 patients treated with aminoglutethimide.

CONCLUSION

Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.
Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma.
Authors: Sparano J A , Fisher R I , Sunderland M , Margolin K , Ernest M L , Sznol M , Atkins M B , Dutcher J P , Micetich K C , Weiss G R
Published: February 2017

PURPOSE

To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-alpha) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design.

PATIENTS AND METHODS

Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 X 10(6) U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 X 10(6) U/m2 per dose, plus IFN-alpha 3 X 10(6) U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report.

RESULTS

Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-alpha (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-alpha (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-alpha arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-alpha arm was less than 25%.

CONCLUSION

Using the preparation, dose, and schedule of IL-2 in our trial, IFN-alpha failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.
Phase I clinical and pharmacokinetic evaluation of high-dose mitoxantrone in combination with cytarabine in patients with acute leukemia.
Authors: Feldman E J , Alberts D S , Arlin Z , Ahmed T , Mittelman A , Baskind P , Peng Y M , Baier M , Plezia P
Published: February 2017

PURPOSE

To determine the maximally tolerated dose of mitoxantrone in combination with cytarabine in patients with acute leukemia and advanced phases of chronic myelogenous leukemia (CML), and to assess the pharmacokinetics of high-dose mitoxantrone in this patient population.

PATIENTS AND METHODS

In a phase I study, 68 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and accelerated- and blastic-phase CML received induction therapy consisting of cytarabine 3 g/m2 by infusion over 3 hours daily for 5 days, with escalating doses of mitoxantrone 40 to 80 mg/m2 over 1 to 2 days by intravenous infusion over 15 minutes. Mitoxantrone pharmacokinetics were evaluated by high-performance liquid chromatography (HPLC) in 15 patients given a single dose of mitoxantrone ranging from 40 to 80 mg/m2 in combination with cytarabine.

RESULTS

Severe, but reversible hyperbilirubinemia (> three times normal) was considered the dose-limiting toxicity, and was observed in 25% of all patients and in 35% of those who received 70 to 80 mg/m2 of mitoxantrone. Other extramedullary toxicity, including cardiac dysfunction, was mild. Myelosuppression was universal and the median time to complete remission (CR) was 28 days (range, 19 to 77). The CR rate for previously untreated and relapsed patients with AML was 85% (17 of 20) and 38% (seven of 18), respectively. Eighty-three percent (15 of 18) of patients with ALL achieved a CR, including all patients with previously untreated disease. Eight of 12 patients with advanced-phase CML achieved a CR. No significant changes in mean mitoxantrone plasma elimination rates (ie, terminal plasma half-life and total-body clearance rate) occurred as the mitoxantrone dose doubled, indicating linear pharmacokinetics.

CONCLUSIONS

The recommended phase II dose of mitoxantrone is 80 mg/m2 administered over 15 minutes as a single intravenous infusion in combination with cytarabine 3 g/m2/d for 5 days. At this dose, high concentrations of mitoxantrone are achievable in vivo to levels that have been shown to be extremely cytotoxic in vitro.
Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.
Authors: Karato A , Sasaki Y , Shinkai T , Eguchi K , Tamura T , Ohe Y , Oshita F , Nishio M , Kunikane H , Arioka H
Published: February 2017

PURPOSE

To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it.

PATIENTS AND METHODS

Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy.

RESULTS

Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown).

CONCLUSION

The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.
Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.
Authors: Chlebowski R T , Blackburn G L , Buzzard I M , Rose D P , Martino S , Khandekar J D , York R M , Jeffery R W , Elashoff R M , Wynder E L
Published: February 2017

PURPOSE

To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer.

PATIENTS AND METHODS

Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling.

RESULTS

Significantly reduced (P < .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P < .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P < .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P < .001).

CONCLUSION

Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.
Patterns of relapse after autologous purged bone marrow transplantation for neuroblastoma: a Childrens Cancer Group pilot study.
Authors: Matthay K K , Atkinson J B , Stram D O , Selch M , Reynolds C P , Seeger R C
Published: February 2017

PURPOSE

The goal of this investigation was to determine if comparing sites of neuroblastoma at relapse after myeloablative chemoradiotherapy and purged autologous bone marrow transplantation (ABMT) with sites of disease at diagnosis and before ABMT could provide insight to the reasons for treatment failure.

PATIENTS AND METHODS

Ninety-nine patients with high-risk neuroblastoma underwent ABMT after induction chemotherapy, surgery +/- local radiation (RT) and then myeloablative therapy with teniposide (or etoposide), melphalan, doxorubicin, cisplatin, and total-body irradiation (TBI).

RESULTS

Forty-one of 84 assessable patients (15 toxic deaths) developed progressive disease 1 to 44 months after ABMT. The overall probability of relapse 36 months after ABMT was 49%. Tumor recurred in primary (n = 22), bone (n = 20), bone marrow (n = 18), lung (n = 3), and other sites (n = 9). Eight patients relapsed in the primary site alone, 14 in primary and distant sites, and 19 in distant sites only. Of 41 patients with progressive disease, 33 have died, with a median interval from relapse to death of 4 months. Both bone and bone marrow involvement at diagnosis correlated with specific relapse in that site (P < .05). Bone marrow tumor content at harvest greater than 0.1% also correlated with bone marrow relapse (P = .001). There was an association between incomplete resection of the primary tumor at diagnosis and relapse in that site (P = .06).

CONCLUSION

Neuroblastoma normally recurs in multiple sites after ABMT, particularly in areas of previous disease. More intensive treatment to known areas of disease (aggressive early surgery, effective myeloablative consolidation therapy) and post-ABMT therapy for minimal residual disease should be studied for their potential to decrease the frequency of relapse.
Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.
Authors: Williams C D , Goldstone A H , Pearce R , Green S , Armitage J O , Carella A , Meloni G
Published: February 2017

PURPOSE

We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study.

PATIENTS AND METHODS

Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis.

RESULTS

The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups.

CONCLUSION

This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.
Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma.
Authors: Hill M , Cunningham D , MacVicar D , Roldan A , Husband J , McCready R , Mansi J , Milan S , Hickish T
Published: February 2017

PURPOSE

This prospective study of patients treated at the Royal Marsden Hospital Lymphoma Unit was designed to evaluate the role of magnetic resonance imaging (MRI) in the assessment of residual masses evident on computed tomographic (CT) scanning following treatment of lymphoma.

PATIENTS AND METHODS

All patients had MRI, gallium-67 single-photon emission CT (67Ga SPECT), and erythrocyte sedimentation rate (ESR) performed within 3 months of completing therapy. Patients were monitored for 1 year posttreatment and observed for signs of relapse. Investigation results were correlated with disease status, and the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) calculated. Time-to-relapse curves were derived and the log-rank test used to determine whether patients with a positive result were more likely to have a relapse within the mass than those with a negative result.

RESULTS

Thirty-four patients were studied, 14 of whom relapsed, 11 within the area of residual mass. Overall, MRI had a high specificity (90%), PPV (71%), and NPV (75%), but poor sensitivity (45%). The results for 67Ga SPECT were similar, apart from lower sensitivity (33%). ESR had inferior performance in predicting relapse compared with the other tests. MRI was the only investigation to show statistical significance (P = .14) in predicting relapse, and this was particularly evident in Hodgkin's lymphoma (P = .003). Combining results of 67Ga SPECT and MRI did not improve predictive power.

CONCLUSION

These data demonstrate that MRI is a valuable tool in the setting of a residual mass after treatment, giving clinically useful prognostic information. 67Ga SPECT also has a role, but is less effective in predicting relapse than MRI.
General information tapes inhibit recall of the cancer consultation.
Authors: Dunn S M , Butow P N , Tattersall M H , Jones Q J , Sheldon J S , Taylor J J , Sumich M D
Published: February 2017

PURPOSE

Studies of tape recordings of cancer consultations have produced conflicting results. At the same time, audiotapes containing general information about cancer are poorly evaluated and are distributed to patients in an ad hoc manner. We compared the effects of both interventions on patient satisfaction, psychologic adjustment, and recall of information following their first consultation with a medical oncologist.

PATIENTS AND METHODS

Patients (n = 142) were randomized to receive (1) an audiotape of their consultation, (2) an audiotape describing cancer in general terms, or (3) no tape. Recall of information was assessed in a structured interview 4 to 20 days after the consultation.

RESULTS

Satisfaction with the consultation increased linearly from no tape to general tape to consultation tape. Satisfaction with the tape itself was higher in patients who received the consultation tape (satisfaction score, 61%) compared with those who received the general tape (43%). Average recall for all groups was 6.4 of the 25 items of information presented, and 2.4 of the six points identified as particularly important by the oncologist. The consultation tape did not improve recall over the no tape control, but the general tape caused a decrease of almost two items in total recall. Spontaneous (ie, unprompted) recall was significantly poorer with the general information tape. Psychologic adjustment to cancer was unaffected.

CONCLUSION

We conclude that individual audiotapes have a limited potential to increase recall of information from the oncology consultation. General information tapes about cancer appear to inhibit recall actively.
Preoperative endoscopic ultrasound can predict the risk of recurrence after operation for gastric carcinoma.
Authors: Smith J W , Brennan M F , Botet J F , Gerdes H , Lightdale C J
Published: February 2017

PURPOSE

Endoscopic ultrasonography (EUS) has been shown to determine accurately the depth of invasion of the stomach wall in gastric carcinoma. We undertook this study to determine if T (tumor) stage as determined by EUS correlated with recurrence after resection and could be used to identify patients preoperatively at high risk for recurrence.

MATERIALS AND METHODS

We reviewed the surgical pathology and obtained follow-up data from the first 50 patients who underwent preoperative EUS for staging of gastric carcinoma. Rotating sector-scan ultrasound endoscopes were used with switchable frequencies of 7.5 MHz and 12 MHz.

RESULTS

Of 50 patients, 43 underwent resection with curative intent and were available for follow-up. The concordance of EUS T stage with pathologic T stage in these patients was 86%. At a median follow-up duration of 25 months, only two of 13 patients with preoperative EUS stage T1 or T2 disease were found to have recurrence, while 23 of 30 patients with EUS stage T3 or T4 disease had recurrence (P = .0002) and 22 died.

CONCLUSION

We conclude that patients with a preoperative EUS stage T1 or T2 are at low risk for postoperative recurrence, while patients with EUS stage T3 or T4 are at high risk for early postoperative recurrence. The latter patients are reasonable candidates for controlled trials of alternative preoperative management programs, such as chemotherapy, in an effort to improve their poor prognosis.
Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103.
Authors: Trimble E L , Adams J D , Vena D , Hawkins M J , Friedman M A , Fisherman J S , Christian M C , Canetta R , Onetto N , Hayn R
Published: February 2017

PURPOSE

To provide an investigational drug, paclitaxel, now commercially available, to women with refractory ovarian cancer and to evaluate response and toxicity in these patients.

PATIENTS AND METHODS

Patients with platinum-refractory ovarian cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3, at least three prior chemotherapy regimens, adequate hepatic and renal function, and no significant cardiac history were eligible. Patients were treated with paclitaxel 135 mg/m2 administered by 24-hour continuous intravenous infusion every 3 weeks.

RESULTS

Leukopenia was the most frequent toxicity, with 78% of patients experiencing grade 3 or 4 toxicity. Other grade 3 and 4 toxicities were less common: fever (33%), infection (12%), thrombocytopenia (8%), vomiting (7%), cardiac (2%), neurologic (2%), and mucositis (1%). Fifteen treatment-related deaths (1.5%) were reported. The objective response rate was 22% (4% complete response [CR], 18% partial response; 95% confidence interval [CI] for overall response, 19% to 25%). The median time to progression from treatment initiation was 7.1 months in responding patients and 4.5 months for all patients. The median survival duration was 8.8 months.

CONCLUSION

Paclitaxel has shown activity in women with platinum-refractory ovarian cancer, and it can be administered with an acceptable safety profile. Further research is needed to determine the optimal role of paclitaxel in the primary and salvage treatment of ovarian cancer.
Phase I trial of recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast in patients with breast cancer receiving cyclophosphamide, doxorubicin, and fluorouracil.
Authors: O'Reilly S E , Gelmon K A , Onetto N , Parente J , Rubinger M , Page R A , Plenderleith I H
Published: February 2017

PURPOSE

To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer.

PATIENTS AND METHODS

Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels.

RESULTS

The 125-micrograms/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250-micrograms/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 10(9)/dL) by 2 or more days in five of six patients. The 500-micrograms/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients.

CONCLUSION

RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.
Bioavailability of low-dose oral etoposide.
Authors: Hande K R , Krozely M G , Greco F A , Hainsworth J D , Johnson D H
Published: February 2017

PURPOSE

To determine the bioavailability of oral etoposide capsules administered at doses of 100 mg and 400 mg.

PATIENTS AND METHODS

The bioavailability of oral etoposide was determined by measuring the area under the etoposide plasma concentration versus time curve (AUC) following intravenous (IV) etoposide administration and comparing that value to the AUC achieved following an oral dose administered 1 day later to the same patient. The bioavailability of a 100-mg oral dose of etoposide was measured on 16 occasions in 11 patients. The bioavailability of a 400-mg dose was determined on 12 occasions in six patients.

RESULTS

The mean (+/- SD) bioavailability following a 100-mg dose of oral etoposide was 76% +/- 22%, which was significantly greater (P < .01) than the mean bioavailability of 48% +/- 18% following a 400-mg oral dose. The coefficient of variation in oral etoposide bioavailability was significant: 29% with a 100-mg oral dose and 37% with a 400-mg dose.

CONCLUSION

Bioavailability of a 100-mg oral etoposide dose is greater than suggested in the package insert from Bristol Laboratories (Evansville, IN). Comparable oral etoposide doses are not uniformly twice that of an IV dose, as suggested by the package insert, but will depend on the final oral dose administered. Bioavailability is better at lower oral etoposide doses. This study confirms the wide interpatient and intrapatient variability in oral etoposide bioavailability.
Secondary cytoreduction for ovarian cancer following cisplatin therapy.
Authors: Segna R A , Dottino P R , Mandeli J P , Konsker K , Cohen C J
Published: February 2017

PURPOSE

This study was undertaken to evaluate the efficacy of secondary surgical cytoreduction in the management of ovarian cancer.

PATIENTS AND METHODS

The cases of 100 patients with recurrent or progressive epithelial ovarian cancer whose initial treatment had been cytoreduction followed by cytotoxic therapy with a cisplatin-based regimen were reviewed. All 100 patients underwent surgery, after recurrence or progression was documented preoperatively, by gynecologic oncologists at the Mount Sinai Medical Center, New York, NY, between 1980 and 1991 with the intention of performing radical tumor reduction.

RESULTS

Sixty-one patients had a secondary cytoreduction that left residual disease less than 2 cm in diameter. The median survival, determined from the date of the secondary cytoreduction to the date of death or last follow-up, is 27.1 months in the optimally treated group and 9.0 months for the 39 patients whose surgery was suboptimal (P = .0001). Other variables associated with statistically significant longer survival, and a significantly higher probability of achieving a successful secondary cytoreduction, included age < or = 55 years at the time of secondary cytoreduction, interval from initial diagnosis to secondary cytoreduction of more than 12 months, residual disease at initial staging laparotomy of less than 2 cm, and a complete clinical response to a cisplatin-based front-line regimen. Multivariate analysis confirms the survival benefit provided by a successful secondary cytoreduction when adjusted for the above variables. There was one postoperative mortality. Ten percent of the successfully cytoreduced patients and 18% of the unsuccessfully cytoreduced patients experienced some degree of postoperative morbidity.

CONCLUSION

These data justify the performance of secondary cytoreductive surgery for patients who develop gross recurrent or progressive ovarian cancer following cisplatin therapy.
Palliative pamidronate treatment in patients with bone metastases from breast cancer.
Authors: van Holten-Verzantvoort A T , Kroon H M , Bijvoet O L , Cleton F J , Beex L V , Blijham G , Hermans J , Neijt J P , Papapoulos S E , Sleeboom H P
Published: February 2017

PURPOSE

An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients.

PATIENTS AND METHODS

Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity. Twenty-nine of 81 pamidronate (HD/LD) patients first received 600 mg/d and were then changed to 300 mg/d; 52 of 81 pamidronate LD patients received 300 mg/d throughout the study. Tumor treatment was unrestricted.

RESULTS

An overall intent-to-treat analysis was performed. In the pamidronate group, the occurrence of hypercalcemia, severe bone pain, and symptomatic impending fractures decreased by 65%, 30%, and 50%, respectively; event-rates of systemic treatment and radiotherapy decreased by 35% (P < or = .02). The event-free period (EFP), radiologic course of disease, and survival did not improve. Subgroup analyses suggested a dose-dependent treatment effect. Compared with their controls, in pamidronate HD/LD patients, events occurred 60% to 90% less frequently (P < or = .03) and the EFP was prolonged (P = .002). In pamidronate LD patients, event-rates decreased by 15% to 45% (P < or = .04). Gastrointestinal toxicity of pamidronate caused a 23% drop-out rate, but other cancer-associated factors seemed to contribute to this toxicity.

CONCLUSION

Pamidronate treatment of breast cancer patients efficaciously reduced skeletal morbidity. The effect appeared to be dose-dependent. Further research on dose and mode of treatment is mandatory.
Pregnancy outcome in patients treated for Hodgkin's disease.
Authors: Aisner J , Wiernik P H , Pearl P
Published: February 2017

PURPOSE

This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkin's disease and to assess the effect of treatment on the children of the treated parents.

MATERIALS AND METHODS

A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children.

RESULTS

Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up > 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children.

CONCLUSIONS

This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population.
Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.
Authors: Tubergen D G , Gilchrist G S , O'Brien R T , Coccia P F , Sather H N , Waskerwitz M J , Hammond G D
Published: February 2017

PURPOSE

This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features.

PATIENTS AND METHODS

We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials.

RESULTS

Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04).

CONCLUSIONS

IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.
Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.
Authors: Marina N M , Rodman J , Shema S J , Bowman L C , Douglass E , Furman W , Santana V M , Hudson M , Wilimas J , Meyer W
Published: February 2017

PURPOSE

The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors.

PATIENTS AND METHODS

To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded.

RESULTS

Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs).

CONCLUSION

The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.
Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma.
Authors: Campbell L A , Seeger R C , Harris R E , Villablanca J G , Matthay K K
Published: February 2017

PURPOSE

This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma.

PATIENTS AND METHODS

Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels.

RESULTS

Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting.

CONCLUSION

This investigation illustrates that response is possible even in an extremely poor-prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs.
Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer.
Authors: Danhauser L L , Freimann J H , Gilchrist T L , Gutterman J U , Hunter C Y , Yeomans A C , Markowitz A B
Published: February 2017

PURPOSE

Enhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated.

PATIENTS AND METHODS

FUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN-a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography.

RESULTS

The maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose-limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +/- 0.35 mumol/L to 1.85 +/- 0.48 mumol/L), elimination half-life (t1/2; mean, 9.7 +/- 4.3 minutes), area under the concentration-versus-time curve (AUC; range, 93 to 224 mumol/L x hours), total-body clearance (CI; range, 1,172 to 3,236 mL/min), or volume of distribution (range, 11.9 to 49.2 L) of FUra. Intrapatient data evaluation revealed a dose-independent effect of rIFN-a. The mean FUra Css after rIFN-a administration (1.31 mumol/L) was greater than that before rIFN-a administration (1.02 mumol/L, P < .0001). FUra Cl after rIFN-a administration was reduced by 20% to 35% compared with use of FUra alone (P < .0001). Patients with a greater than 20% decrease in FUra Cl had a fourfold greater incidence of diarrhea.

CONCLUSION

rIFN-a reduces FUra Cl and, consequently, increases FUra-associated toxicity. Phase II studies of FUra and rIFN-a seem to be warranted.
Characteristics of women at risk for psychosocial distress in the year after breast cancer.
Authors: Schag C A , Ganz P A , Polinsky M L , Fred C , Hirji K , Petersen L
Published: February 2017

PURPOSE

To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment.

PATIENTS AND METHODS

A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups.

RESULTS

The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction.

CONCLUSION

The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored.
Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.
Authors: Wolfrom C , Hartmann R , Fengler R , Brühmüller S , Ingwersen A , Henze G
Published: February 2017

PURPOSE

Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial.

PATIENTS AND METHODS

Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54.

RESULTS

Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR.

CONCLUSION

Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.