bluuebunny/crossref_metadata_2025 huggingface dataset:
Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.
Authors: Bolis G , Favalli G , Danese S , Zanaboni F , Mangili G , Scarabelli C , Tateo S , Valsecchi M G , Scarfone G , Richiardi G , Frigerio L , Melpignano M , Villa A , Parazzini F
Published: February 2017

PURPOSE

To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial.

PATIENTS AND METHODS

Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses.

RESULTS

A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96).

CONCLUSION

This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.
Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting.
Authors: Gordon A N , Stringer C A , Matthews C M , Willis D L , Nemunaitis J
Published: February 2017

PURPOSE

To determine the maximum-tolerable dose (MTD) of paclitaxel in a phase I dose-escalation study when combined with cisplatin in patients with advanced ovarian cancer receiving filgrastim for prophylaxis of myelosuppression.

PATIENTS AND METHODS

A total of 23 patients with stage II (bulky residual), III, or IV epithelial ovarian cancer were treated (following debulking surgery) with paclitaxel as a 3-hour infusion followed by cisplatin (75 mg/m2) administered over 4 hours on day 1, repeated every 21 days for six cycles. Filgrastim (5 micrograms/kg/d) was administered subcutaneously (SC) beginning on day 2 of each cycle through neutrophil recovery (absolute neutrophil count [ANC] > 10,000/microL). Patients were assigned to one of six escalating dose levels of paclitaxel: 150 (n = 3), 175 (n = 3), 200 (n = 3), 225 (n = 4), 250 (n = 4), and 275 mg/m2 (n = 6).

RESULTS

At each paclitaxel dose level (150, 175, 200, 225, 250, and 275 mg/m2), the numbers of patients who completed six cycles without dose reduction were three (100%), three (100%), two (66%), two (50%), three (75%), and zero (0%), respectively. The numbers of patients who experienced a grade III/IV adverse event (hematologic or nonhematologic) were zero (0%), two (66%), two (66%), one (25%), four (100%), and five (80%), respectively. Reasons for dose reduction included neurotoxicity (225 mg/m2, n = 1; 275 mg/m2, n = 2), neutropenia (225 mg/m2, n = 2), diarrhea (275 mg/m2, n = 2), and nephrotoxicity (225 mg/m2, n = 1). Reasons for not completing six cycles at full or reduced dose included neuropathy (200, 225, and 275 mg/m2, n = 1 each) physician request (275 mg/m2, n = 1), and death (275 mg/m2, n = 1). Hematopoietic toxicity was minimal. Six patients developed grade III/IV neutropenia. No patient developed thrombocytopenia below a level of 50,000/microL.

CONCLUSION

The MTD of paclitaxel was determined to be 225 mg/m2 when administered as a 3-hour infusion and combined with cisplatin (75 mg/m2). Nonhematologic dose-limiting toxicities were neuropathy and diarrhea. The neuropathy often had a rapid onset, especially at the higher dose levels.
Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors: pharmacokinetics, clinical outcome, and comparison of formulations.
Authors: Kohn E C , Figg W D , Sarosy G A , Bauer K S , Davis P A , Soltis M J , Thompkins A , Liotta L A , Reed E
Published: February 2017

PURPOSE

Cytostatic agents targeted against angiogenesis and tumor cell invasive potential form a new class of investigational drugs. Orally administered carboxyamidotriazole (CAI) (NSC609974) is both antiangiogenic and antimetastatic. An encapsulated micronized powder formulation has been developed to optimize CAI administration. A phase I dose escalation trial with pharmacokinetic analysis has been performed.

PATIENTS AND METHODS

Twenty-one patients with refractory solid tumors and good end organ function and performance status were enrolled onto the study. Patients received a test dose followed 1 week later by daily administration of CAI in the encapsulated micronized formulation at doses of 100 to 350 mg/m2. Patients remained on CAI until disease progression or dose-limiting toxicity. Plasma samples were taken to characterize the pharmacokinetic parameters of this formulation of CAI.

RESULTS

All patients were assessable for toxicity and 18 were assessable for pharmacokinetics and response analysis. Grade 1 and 2 gastrointestinal side effects were observed in up to 50% of patients. Dose-limiting toxicity was observed in both patients treated at 350 mg/m2/d, consisting of reversible grade 2 to 3 cerebellar ataxia (n = 1) and confusion (n = 1). One minor response (MR) was observed in a patient with renal cell carcinoma and another nine patients had disease stabilization (MR + SD = 47%). Pharmacokinetic analysis demonstrated reduced bioavailability (58% reduction) compared with the PEG-400 liquid formulation previously reported.

CONCLUSION

The better toxicity profile of encapsulated micronized CAI with similar frequency of disease stabilization and ease of administration compared with the liquid or gelatin capsule, suggests that the micronized formulation is a preferable formulation for subsequent studies. A dose of 300 mg/m2/d is proposed for phase II investigations.
Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of life in colorectal liver metastasis patients.
Authors: Earlam S , Glover C , Davies M , Fordy C , Allen-Mersh T G
Published: February 2017

PURPOSE

Since systemic and regional (HAI) fluorinated pyrimidine chemotherapies offer similar survival benefit in treatment of colorectal liver metastases (CLM), we sought to identify their impact on quality of life (QoL), which might be a useful indicator of treatment preference.

METHODS

We compared QoL in 135 CLM patients managed by symptom control (n = 49 patients), systemic fluorouracil (5FU)/folinic acid (n = 35), or hepatic arterial floxuridine (FUDR) (n = 51). Full blood count and liver function tests, World Health Organization (WHO) toxicity criteria, and QoL (Rotterdam Symptom Checklist [RSC], the Sickness Impact Profile [SIP], and the Hospital Anxiety and Depression scale [HAD]) were measured monthly in all patients.

RESULTS

The HAD anxiety score was significantly increased in symptom control compared with chemotherapy patients 1 month after randomization. There was a significant increase in RSC physical score (repeated measures, P = .05), and in scores for sore mouth (P < .01), dry mouth (P < .01), and tingling hands and feet (P < .01) in systemic chemotherapy compared with symptom control patients. Significant QoL differences (repeated measures and Mann-Whitney U [MWU]) between HAI and symptom control patients were not detected. Systemic chemotherapy patients lived for significantly longer (log-rank test, P < or = .0001) with abnormal HAD anxiety, RSC psychosocial, or RSC sore mouth scores compared with HAI patients, but there were no overall survival differences.

CONCLUSION

Randomization to symptom control only was associated with increased anxiety. QoL with systemic chemotherapy was impaired by side effects. HAI was associated with similar survival to systemic chemotherapy but with better sustained QoL.
Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114.
Authors: Tepper J E , O'Connell M J , Petroni G R , Hollis D , Cooke E , Benson A B , Cummings B , Gunderson L L , Macdonald J S , Martenson J A
Published: February 2017

PURPOSE

The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole.

METHODS

A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole.

RESULTS

With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation.

CONCLUSION

There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.
Why has induction chemotherapy for advanced head and neck cancer become a United States community standard of practice?
Authors: Harari P M
Published: February 2017

PURPOSE

Induction chemotherapy for advanced head and neck (H&N) cancer has been studied in clinical trials for more than two decades without clear demonstration of benefit for locoregional tumor control or overall patient survival. Nonetheless, its use has become a common community standard of practice in the United States (US). This report examines some of the factors that may have contributed to this phenomenon.

MATERIALS AND METHODS

A mail survey was conducted of 300 US community cancer specialists (equally divided among otolaryngologists, radiation oncologists, and medical oncologists) to solicit their most frequent therapy approach for patients with locoregionally advanced, nonmetastatic H&N cancer. The rationale for selection of treatment strategy was identified by each respondent.

RESULTS

Two hundred eighteen physicians (73%) completed and returned the survey, representing 47 US states. The single most common treatment approach reported for patients with locoregionally advanced H&N cancer was that of sequential chemoradiation (61%), specifically, induction chemotherapy with fluorouracil (5-FU)/cisplatin followed by radiation therapy. Four percent of respondents indicated that induction chemotherapy was administered within the context of a controlled clinical trial, whereas 96% indicated that therapy was administered off study. The primary objectives cited by respondents for the use of induction chemotherapy included the desire to improve locoregional tumor control (67%), to improve overall survival (56%), to maintain a spirit of multidisciplinary care (34%), to improve quality of life (29%), and to decrease distant metastases (26%).

CONCLUSION

Review of the published trials between 1970 and 1995 and of the published meta-analyses show no clear evidence for an improvement in locoregional tumor control or survival for H&N cancer patients treated with 5-FU/cisplatin induction chemotherapy regimens. Nonetheless, this induction chemotherapy approach for advanced H&N cancer patients has become a dominant community practice in the US. Factors that may have contributed to this paradox are reviewed.
Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma?
Authors: Lenzi R , Hess K R , Abbruzzese M C , Raber M N , Ordoñez N G , Abbruzzese J L
Published: February 2017

PURPOSE

The objectives of this study were to assess clinical outcomes and prognostic factors in unselected, consecutive patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA).

PATIENTS AND METHODS

The 1,400 patients analyzed were referred to our unknown-primary tumor (UPT) clinic from January 1, 1987 through July 31, 1994. Clinical data from these patients were entered into a computerized data base for storage, retrieval, and analysis. Survival was measured from the time of diagnosis; survival distribution was estimated using the product-limit method. Multivariate survival analyses were performed using proportional hazards regression and by recursive partitioning.

RESULTS

Nine hundred seventy-seven patients were diagnosed with unknown-primary carcinoma (UPC) and 337 of these patients had PDC or PDA. No clinical differences were identified among patients with PDC, PDA, or UPC patients with other carcinoma or adenocarcinoma subtypes. PDC patients enjoyed better survival than PDA patients. Poor cellular differentiation was not an important prognostic variable. Variables predictive of survival included lymph node metastases, sex, number of metastatic sites, histology (PDC v PDA), and age. Although chemotherapy did not appear to influence survival for the entire group of PDC or PDA patients, a subset of patients with good prognostic features experienced median survival durations of up to 40 months.

CONCLUSION

The long median survival and chemotherapy responsiveness of UPC patients with PDC and PDA could not be confirmed. However, subpopulations with prolonged median survival durations could be defined, and the value of chemotherapy in this group remains to be determined. Identification and exclusion of treatable or slow-growing malignancies may account for the poor survival of the PDC and PDA patients reported in this study.
Tobacco use among pediatric cancer patients: recommendations for developing clinical smoking interventions.
Authors: Tyc V L , Hudson M M , Hinds P , Elliott V , Kibby M Y
Published: February 2017

PURPOSE AND METHODS: The current status of tobacco use among young cancer patients and the acute and chronic complications associated with tobacco use in these patients is reviewed. RESULTS AND CONCLUSION: Studies report that adolescent cancer survivors use tobacco as much as their peers who have never been treated for cancer, despite the adverse consequences of engaging in this unhealthy habit. Health care professionals have the opportunity and responsibility to incorporate tobacco counseling as a routine component of medical care delivery. Nurse/physician-delivered smoking interventions have been found to promote smoking cessation in adults, although little effort has been devoted to the development of similarly effective smoking interventions for pediatric cancer patients who smoke. Components of existing smoking prevention/cessation curricula from successful school-based interventions and physician-delivered smoking interventions can be adapted and tailored to pediatric cancer patients in medical settings. Smoking interventions that educate patients about their increased vulnerability to tobacco-related consequences, relative to their healthy peers, may have an enhanced impact. Guidelines for conducting a comprehensive assessment of tobacco use and implementing smoking interventions with pediatric cancer patients is provided. Strategies for modifying the cancer patient's perceived vulnerability to tobacco-related consequences is also discussed.
Acyclovir prophylaxis and fever during remission-induction therapy of patients with acute myeloid leukemia: a randomized, double-blind, placebo-controlled trial.
Authors: Bergmann O J , Mogensen S C , Ellermann-Eriksen S , Ellegaard J
Published: February 2017

PURPOSE

A randomized, double-blind, placebo-controlled trial was performed to estimate the preventive effect of the antiherpetic drug acyclovir on fever, incidence of bacteremia, use of antibiotics, and presentation of infections in patients with acute myeloid leukemia (AML).

PATIENTS AND METHODS

Ninety herpes simplex virus (HSV)-seropositive patients aged 18 to 84 years were included. Forty-five patients received acyclovir (800 mg by mouth daily) and 45 placebo. The patients were examined daily for 28 days from the initiation of remission-induction chemotherapy.

RESULTS

Fever developed in all patients in both groups. Acyclovir prophylaxis postponed the development of an oral temperature > or = 38.0 degrees C by 3 days (95% confidence interval [CI], 1 to 4 days; P = .03) and the initiation of antibacterial treatment by 3 days (95% CI, 1 to 5 days; P = .008). The duration of fever, use of antibacterial treatment, incidence of bacteremia, and need for systemic antifungal therapy were not affected by acyclovir prophylaxis. At fever development, acyclovir prophylaxis affected the incidence and localization pattern of oral ulcers. Thus, in the acyclovir group, the number of nonfungal oral infections was reduced (relative risk, 0.45 [95% CI, 0.24 to 0.85]) and mainly located on the soft palate (relative risk, 2.49 [95% CI, 1.19 to 5.22]).

CONCLUSION

Acyclovir prophylaxis has an impact on fever development, but not on the duration of fever or the need for antibiotics. It does not reduce the incidence of bacteremia, but the presentation of acute oral infections is changed.
Sentinel lymphadenectomy in breast cancer.
Authors: Giuliano A E , Jones R C , Brennan M , Statman R
Published: February 2017

PURPOSE

We previously demonstrated increased detection of axillary metastases using sentinel lymphadenectomy (SLND) and immunohistochemistry. These methods have evolved and we now report our current use of these techniques and our most recent results of axillary staging with SLND.

PATIENTS AND METHODS

One hundred seven consecutive women (previously unreported) with breast cancer underwent SLND followed by completion axillary lymphadenectomy (ALND). All sentinel nodes were examined intraoperatively with frozen section and postoperatively with hematoxylin and eosin staining (H&E) plus immunohistochemical staining (IHC) using antibody to cytokeratin. The nonsentinel axillary nodes were examined with H&E, but not IHC.

RESULTS

The median age was 56.6 years (range, 28 to 90). Most patients (58.9%) were postmenopausal, most primary tumors (62.6%) were palpable, and most operations (86.9%) were breast-conserving. The mean tumor size was 2.11 +/- 1.38 cm. Sentinel nodes were identified in 100 patients: 42 patients had metastases in sentinel nodes; of these, 28 (66.7%) had no other involved axillary nodes. On average, 1.8 +/- 1.1 sentinel nodes were examined and 20.3 +/- 7.8 nonsentinel nodes were removed. Of seven patients with no identified sentinel nodes, six had a tumor-negative axilla. SLND was 100% predictive of axillary status in these 100 women.

CONCLUSION

In this population of breast cancer patients, SLND with frozen section and IHC was a minimally invasive, highly accurate intraoperative method of axillary staging. We are evaluating the elimination of routine ALND for sentinel-node negative women to minimize the morbidity associated with standard dissections. The ability to identify node-negative patients without ALND would be a welcome addition to the management of women with breast cancer.
Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx.
Authors: Mendenhall W M , Parsons J T , Mancuso A A , Pameijer F J , Stringer S P , Cassisi N J
Published: February 2017

PURPOSE

To report the results of radiotherapy alone for stage T3 squamous cell carcinoma of the true vocal cord and compare these data with those obtained with other treatment modalities.

METHODS AND MATERIALS

Seventy-five patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy alone (73 patients) or followed by a planned neck dissection (two patients) at the University of Florida between September 1966 and August 1994. No patient received adjuvant chemotherapy. All patients were monitored for at least 2 years and 85% had a minimum follow-up duration of 5 years. No patient was lost to follow-up evaluation.

RESULTS

The 5-year local control and ultimate local control rates were 63% and 86%, respectively. The volume of the primary tumor (which was calculated on pretreatment computed tomographic [CT] scans in 38 patients) was inversely related to local control with larynx preservation: < or = 3.5 cm3, 20 of 23 (87%) versus greater than 3.5 cm3, four of 14 (29%) (P = .0005). There was no apparent relationship between local control after radiotherapy as a function of whether the vocal cord regained mobility or remained fixed during or shortly after completion of treatment. The 5-year absolute and cause-specific survival rates were 54% and 78%, respectively. Multivariate analysis showed that pretreatment tracheostomy was significantly related to diminished cause-specific survival (P = .0345).

CONCLUSION

Radiotherapy alone results in long-term local-regional control and survival rates that are comparable to those obtained with surgery. It is unclear whether induction or concomitant chemotherapy is associated with improved local-regional control and survival compared with radiotherapy alone.
Imaging of estrogen receptors in primary and metastatic breast cancer patients with iodine-123-labeled Z-MIVE.
Authors: Rijks L J , Bakker P J , van Tienhoven G , Noorduyn L A , Boer G J , Rietbroek R C , Taat C W , Janssen A G , Veenhof C H , van Royen E A
Published: February 2017

PURPOSE

To evaluate the feasibility of noninvasive imaging of estrogen receptors (ERs) in primary and metastatic breast cancer with the iodine-123-labeled ER-specific ligand cis-11beta-methoxy-17alpha-iodovinylestradiol-17beta (Z-[123I]MIVE) using conventional nuclear medicine techniques.

PATIENTS AND METHODS

Z-[123I]MIVE planar scintigraphy and single-photon emission computed tomography (SPECT) were performed in 12 patients with proven primary breast cancer and 13 patients with proven or from other imaging modalities evident bone, liver, lung, pleura and/or lymph node metastases. The results were compared with those of ER immunohistochemistry (IHC). Blocking studies with the antiestrogen tamoxifen were performed to test whether Z-[123I]MIVE tumor uptake was ER-mediated.

RESULTS

Planar imaging showed uptake in 11 of 12 primary carcinomas. ER IHC performed for nine of these was positive. For the planar scintigraphy-negative patient, SPECT was faintly positive, but ER IHC negative (agreement, 90%). In nine of 13 metastatic patients, planar scintigraphy was positive. The agreement between the results of ER IHC on the original primary tumor and of Z-[123I]MIVE scintigraphy was 82%. Specificity of tumor Z-[123I]MIVE uptake was established by complete blockade of uptake by tamoxifen, except in two patients who showed progressive disease. Z-[123I]MIVE scintigraphy also enabled discriminating metastases from confounding nonmalignant abnormalities of the bone scan.

CONCLUSION

Z-[123I]MIVE scintigraphy shows high sensitivity and specificity for the detection of ER-positive breast cancer. This may have impact on diagnostic possibilities and therapeutic management. Since ER imaging shows the functional status, addressing known intratumoral and intertumoral ER heterogeneity, it may improve the characterization of disease and the selection of patients who may benefit from hormonal therapy.
Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma.
Authors: Imazano Y , Takebayashi Y , Nishiyama K , Akiba S , Miyadera K , Yamada Y , Akiyama S , Ohi Y
Published: February 2017

PURPOSE

Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We examined whether TP expression in renal cell carcinoma (RCC) is associated with microvessel density as a marker of angiogenesis, clinicopathologic characteristics, and outcome.

PATIENTS AND METHODS

The enzymatic activity and expression of TP were examined in 18 RCCs and 19 kidney tissues not grossly involved with tumor from 24 patients with 13 paired samples and 11 unpaired samples by spectrophotometry and immunoblotting. The relationship between TP expression and microvessel density was assessed by immunohistochemistry in 133 RCCs.

RESULTS

The median enzymatic activity of TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues (P < .001). Similar results were obtained by immunoblot analysis. According to the TP staining profile, tumors were classified as no or low, intermediate, or high TP-expressing tumors. TP positivity was significantly correlated with microvessel density. TP expression was correlated with tumor grade, but there was no significant association between TP expression and other clinicopathologic characteristics. TP expression as a prognostic variable was studied using Cox's proportional hazards model. TP overexpression was an independent prognostic factor (hazards ratio, 3.95; 95% confidence interval, 0.98 to 15.89; P = .039) as were nodal category, metastases category, tumor grade, and venous invasion.

CONCLUSION

These findings suggest that TP expression is correlated with microvessel density in RCC and is an unfavorable independent prognostic factor. The future development and characterization of TP inhibitors may provide a novel approach to the therapy of RCC.
Limitations of reverse-transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow.
Authors: Zippelius A , Kufer P , Honold G , Köllermann M W , Oberneder R , Schlimok G , Riethmüller G , Pantel K
Published: February 2017

PURPOSE

This study was designed to evaluate the potential of reverse-transcriptase polymerase chain reaction (RT-PCR) analyses for the detection of micrometastatic carcinoma cells in bone marrow (BM).

PATIENTS AND METHODS

The specificity of RT-PCR assays with primers specific for various tumor-associated and organ-specific mRNA species was examined by analysis of 53 BM aspirates from control patients with no epithelial malignancy. In addition, BM samples from 63 patients with prostate cancer (n = 53) or breast cancer (n = 10) were analyzed by RT-PCR with primers specific for prostate-specific antigen (PSA) mRNA. As a reference method, all samples were analyzed simultaneously by an established immunocytochemical assay, using monoclonal antibodies (mAbs) against cytokeratins (CK) for tumor-cell detection.

RESULTS

Seven of eight marker species could be detected in a considerable number of BM samples from control patients: epithelial glycoprotein-40 (EGP-40; 53 of 53 samples), desmoplakin I (DPI I; five of five), carcinoembryonic antigen (CEA; five of 19), erb-B2 (five of seven), erb-B3 (six of seven), prostate-specific membrane antigen (PSM; four of nine), and CK18 (five of seven). Only PSA mRNA was not detected in any of the 53 control BM samples. In serial dilution experiments, the PSA RT-PCR assay was able to detect five LNCaP prostate carcinoma cells in 4 x 10(6) BM cells. CK-positive cells were found in 20 patients (37.7%) with prostate cancer, while PSA mRNA was found in only 15 (28.3%; P = .04). Moreover, despite the recent observation that PSA is also expressed in mammary carcinomas, none of the 10 CK-positive BM samples were PSA mRNA-positive.

CONCLUSION

Limiting factors in the detection of micrometastatic tumor cells by RT-PCR are (1) the illegitimate transcription of tumor-associated or epithelial-specific genes in hematopoietic cells, and (2) the deficient expression of the marker gene in micrometastatic tumor cells.
Low-dose urokinase infusions to treat fibrinous obstruction of venous access devices in cancer patients.
Authors: Horne M K , Mayo D J
Published: February 2017

PURPOSE

This study was undertaken to determine the role of low-dose urokinase infusions in treating fibrinous occlusions of venous access devices (VADs) in cancer patients.

PATIENTS AND METHODS

Forty-two patients with VAD occlusions refractory to routine urokinase instillations were documented by x-ray (cathetergram) to have fibrin sleeves at the catheter tips. They were randomized to receive infusions of either urokinase (40,000 U/h) or urokinase with heparin (320 U/h) through their catheters. After 1, 3, 6, and 12 hours of treatment, the function of the VADs was reassessed. Whenever the obstruction had been relieved, the infusion was stopped and a repeat cathetergram was performed. The status of the unoccluded catheters was followed to determine the longevity of the restored function.

RESULTS

Twenty-one catheters were treated with urokinase alone and 21 with the combination of urokinase and heparin. In each group, 16 VADs opened within 12 hours of treatment and five did not. By actuarial analysis, the probability was only 0.28 that a reopened catheter would reocclude within 6 months.

CONCLUSION

Low-dose urokinase infusions can restore function to the majority of catheters occluded by fibrin sleeves. Adding heparin to the urokinase does not enhance the efficacy of the infusions. The restored function often persists until the VADs are removed.
Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia.
Authors: Del Mastro L , Venturini M , Lionetto R , Garrone O , Melioli G , Pasquetti W , Sertoli M R , Bertelli G , Canavese G , Costantini M , Rosso R
Published: February 2017

PURPOSE

Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy.

PATIENTS AND METHODS

Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11.

RESULTS

Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001).

CONCLUSION

EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.
Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.
Authors: Dinndorf P A , Avramis V I , Wiersma S , Krailo M D , Liu-Mares W , Seibel N L , Sato J K , Mosher R B , Kelleher J F , Reaman G H
Published: February 2017

PURPOSE

The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922) to determine a tolerable dose of idarubicin given with fludarabine and cytarabine in children with relapsed or refractory leukemia. The phase I study was extended to a limited phase II study to assess the activity of this combination in children with acute myelogenous leukemia (AML).

PATIENTS AND METHODS

This was a multiinstitutional study within the CCG. Eleven patients were entered onto the phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of fludarabine and cytarabine determined in a previous study was a fludarabine loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5 mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101 mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12 mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial included 10 additional patients with relapsed or refractory AML.

RESULTS

A dose of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and cytarabine was tolerated. The major toxicity encountered was hematologic. Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia, and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2 idarubicin) achieved a complete remission (CR).

CONCLUSION

This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.
Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.
Authors: Gajjar A , Sanford R A , Heideman R , Jenkins J J , Walter A , Li Y , Langston J W , Muhlbauer M , Boyett J M , Kun L E
Published: February 2017

PURPOSE

To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma.

PATIENTS AND METHODS

Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four.

RESULTS

The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors.

CONCLUSION

The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.
Prognostic factors associated with long-term survival for retroperitoneal sarcoma: implications for management.
Authors: Heslin M J , Lewis J J , Nadler E , Newman E , Woodruff J M , Casper E S , Leung D , Brennan M F
Published: February 2017

PURPOSE

Retroperitoneal soft tissue sarcomas are rare tumors. Studies characterizing long-term follow-up and patterns of recurrence are limited. The purpose of this analysis is to identify patterns of recurrence and prognostic factors associated with long-term survival after resection of retroperitoneal soft tissue sarcomas.

METHODS

Between July 1, 1982, and June 30, 1990, 198 adult patients were identified from our prospective soft tissue sarcoma database carrying the diagnosis of retroperitoneal soft tissue sarcoma who were eligible for > or = 5 years of follow-up. Of these, 48 patients (25%) were documented to be alive > or = 5 years from the time of operation. Statistical analysis was by log-rank or Wilcoxon test for univariate analysis. Multivariate analysis was by the Cox model.

RESULTS

The recurrence rate during the follow-up period was approximately 5% per year from the time of initial operation. Of the patients who were disease-free for > or = 5 years from initial surgery, 40% recurred by 10 years. Radiation therapy was the only factor significant (P = .02) for a reduction in the risk of local recurrence. Age < or = 50 years and high-grade tumors were significant factors (P = .003 and .009, respectively) for an increased risk of distant metastasis. Incomplete gross resection was the only factor significant for an increased risk of tumor mortality (P = .003).

CONCLUSION

Complete surgical resection at the time of primary presentation is likely to afford the best chance for long-term survival. With long-term follow-up, it is clear that recurrence will continue to occur, and a 5-year disease-free interval is not a cure. Patients with an incomplete initial resection, age less than 50 years, and high-grade tumors are candidates for investigational adjuvant therapy.
Immunocytochemical markers in stage I lung cancer: relevance to prognosis.
Authors: Pastorino U , Andreola S , Tagliabue E , Pezzella F , Incarbone M , Sozzi G , Buyse M , Menard S , Pierotti M , Rilke F
Published: February 2017

PURPOSE

This study investigated the frequency of the expression and prognostic significance of a panel of immunocytochemical markers in resected non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

A total of 515 cases of pathologic stage I NSCLC were analyzed. The median follow-up time of surviving patients was 102 months. The following immunocytochemical markers were tested: blood group A and precursors of blood antigens; laminin receptor; c-erbB1/epidermal growth factor receptor (EGFR) and c-erbB2/Neu; BCl2; p53; and angiogenesis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biologic markers using the Cox model for multivariate analysis.

RESULTS

The pathologic tumor extension (pT) represented the most powerful prognostic factor for survival (P = .0008) and time to recurrence (P = .0007). None of the immunocytochemical markers emerged as an independent predictive factor for survival. Bcl2-positive tumors showed a better time to recurrence (P = .03), but the difference lost statistical significance in the multivariate analysis. Of interest, in the group of 137 patients classified as pT1N0, both EGFR expression and nonangiogenic type of vascular pattern were associated with a poorer survival (P = .02). However, data derived from subset analysis must be interpreted cautiously.

CONCLUSION

Our findings do not support a relevant prognostic role of immunocytochemical markers in NSCLC. The evidence is not sufficient to alter clinical practice or even to restrict clinical trials of adjuvant treatments to predefined biologic subsets of patients.
Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.
Authors: Graus F , Dalmou J , Reñé R , Tora M , Malats N , Verschuuren J J , Cardenal F , Viñolas N , Garcia del Muro J , Vadell C , Mason W P , Rosell R , Posner J B , Real F X
Published: February 2017

PURPOSE

Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb.

METHODS

Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen.

RESULTS

HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival.

CONCLUSION

The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.
Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.
Authors: Bastion Y , Blay J Y , Divine M , Brice P , Bordessoule D , Sebban C , Blanc M , Tilly H , Lederlin P , Deconinck E , Salles B , Dumontet C , Brière J , Coiffier B
Published: February 2017

PURPOSE

To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma.

PATIENTS AND METHODS

Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks.

RESULTS

The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death.

CONCLUSION

Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.
Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation therapy in acute myeloid leukemia: a double-blind controlled study.
Authors: Ohno R , Miyawaki S , Hatake K , Kuriyama K , Saito K , Kanamaru A , Kobayashi T , Kodera Y , Nishikawa K , Matsuda S , Yamada O , Omoto E , Takeyama H , Tsukuda K , Asou N , Tanimoto M , Shiozaki H , Tomonaga M , Masaoka T , Miura Y , Takaku F , Ohashi Y , Motoyoshi K
Published: February 2017

PURPOSE

To determine whether macrophage colony-stimulating factor (M-CSF) reduces the incidence and duration of febrile neutropenia during three courses of intensive consolidation therapy and whether it shortens time to complete consolidation therapy.

PATIENTS AND METHODS

In 198 adult patients with acute myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or placebo was administered from 1 day after the end of each consolidation chemotherapy for 14 days.

RESULTS

The duration and incidence of febrile neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065), respectively, in 88 assessable patients in the M-CSF group compared with those in 94 assessable patients in the placebo group. Patients in the M-CSF group had 565 days and 133 episodes of febrile neutropenia during 7,901 days at risk, while patients in the placebo group had 977 days and 185 episodes during 9,077 days at risk. The median period required to finish the three courses of consolidation therapy was 93 days in the M-CSF group, which was significantly shorter than 110 days in placebo group (P = .0050). In the M-CSF group, the recovery of neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364, respectively), the administration of systemic antimicrobial agents tended to be less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the total volume of transfused platelets (P = .0292) were significantly less. However, there was no significant difference in the disease-free survival.

CONCLUSION

M-CSF significantly reduced the incidence and duration of febrile neutropenia during the intensive consolidation therapy, and shortened the time to complete consolidation chemotherapy in AML.