bluuebunny/crossref_metadata_2025 huggingface dataset:
Polloneite, a new complex Pb(-Ag)-As-Sb sulfosalt from the Pollone mine, Apuan Alps, Tuscany, Italy
Authors: Topa Dan , Keutsch Frank N. , Makovicky Emil , Kolitsch Uwe , Paar Werner
Published: February 2017

Polloneite, ideally AgPb46As26Sb23S120, is a new N = 4 member of the sartorite homologous series. It occurs in a matrix of baryte from the Pizzone level of the Pollone baryte-pyrite-(Pb-Zn-Ag) deposit at Valdicastello Carducci, near Pietrasanta, in the Apuan Alps, Tuscany, Italy, as anhedral grains up to 0.5 mm across. The mineral is opaque, greyish black with a metallic lustre. In reflected light polloneite is white, bireflectance is moderate. Internal reflections are absent. Under crossed polars, anisotropism is moderate with rotation tints in brown-violet and deep grey. The reflectance data (%, air) are: 30.2, 42.4 at 470 nm, 28.8, 41.0 at 546 nm, 27.9, 39.8 at 589 nm and 26.0, 37.4 at 650 nm. Mohs hardness is 3–3½, microhardness VHN50exhibits a mean value of 200 kg mm-2. The average results of 15 electronmicroprobe analyses of three grains are Ag 0.71(5), Pb 52.05(21), As 10.61(22), Sb 15.40(12), S 21.16(8), total 99.92(15) wt.%, corresponding to Ag1.20Pb45.76As25.79Sb23.04S120.21(on the basis of Me + S = 216 apfu). The simplified formula AgPb46As26Sb23S120is in accordance with the results of a crystal structure determination. The calculated density is 5.77 g cm–3. Polloneite is monoclinic, space group P21, a = 8.413(2), b = 25.901(5), c = 23.818(5) Å, β = 90.01(3)°, V = 5189.8(18)Å3, Z = 1. The strongest eight lines in the calculated powder-diffraction pattern [d in Å(I)hkl] are 3.795(100)(026), 3.414(60)(233), 3.238(69)(080), 3.020(97)(253), 2.922(82)(066), 2.738(73)(236), 2.375(79)(290) and 2.103(64)(400). Polloneite is a new N = 4 member of the sartorite homologous series with substantial Sb and small, but important, Ag content. It is a three-fold superstructure with a tripled unit-cell parameter, 7.9 Å, of sartorite homologues. In the As-Sb rich slabs, several types of crankshaft chains and isolated (As,Sb)–S polyhedra occur. A sequence of three different, tightly bonded double-layer fragments (broad ribbons) contains two asymmetric fragments with long crankshaft chains whereas the third fragment type, with Ag, contains small mirror-symmetrical metalloid groups and no crankshaft chains. This configuration can potentially cause order-disorder phenomena in the structure. The threefold superstructure and the mixed As-Sb character distinguish polloneite from veenite and from dufrénoysite, respectively.
What’s in a Prerequisite? A Mixed-Methods Approach to Identifying the Impact of a Prerequisite Course
Authors: Sato Brian K. , Lee Amanda K. , Alam Usman , Dang Jennifer V. , Dacanay Samantha J. , Morgado Pedro , Pirino Giorgia , Brunner Jo Ellen , Castillo Leanne A. , Chan Valerie W. , Sandholtz Judith H.
Published: February 2017

Despite the ubiquity of prerequisites in undergraduate science, technology, engineering, and mathematics curricula, there has been minimal effort to assess their value in a data-driven manner. Using both quantitative and qualitative data, we examined the impact of prerequisites in the context of a microbiology lecture and lab course pairing. Through interviews and an online survey, students highlighted a number of positive attributes of prerequisites, including their role in knowledge acquisition, along with negative impacts, such as perhaps needlessly increasing time to degree and adding to the cost of education. We also identified a number of reasons why individuals do or do not enroll in prerequisite courses, many of which were not related to student learning. In our particular curriculum, students did not believe the microbiology lecture course impacted success in the lab, which agrees with our analysis of lab course performance using a previously established “familiarity” scale. These conclusions highlight the importance of soliciting and analyzing student feedback, and triangulating these data with quantitative performance metrics to assess the state of science, technology, engineering, and mathematics curricula.
Design and results of phase I cancer clinical trials: three-year experience at M.D. Anderson Cancer Center.
Authors: Smith T L , Lee J J , Kantarjian H M , Legha S S , Raber M N
Published: February 2017

PURPOSE

Alternatives to the standard design for conducting phase I trials are proposed with increasing frequency. This study was undertaken to determine how phase I trials are currently conducted and to provide a basis for evaluation of evolving methodology.

SUBJECTS AND METHODS

All published phase I trials from a single institution over a 3-year period were reviewed to determine the method of selection of the recommended dose for a phase II trial of a new agent, type and extent of toxicity, number of patients treated at the recommended dose, and clinical response.

RESULTS

All 23 published trials used the standard method of entering cohorts of patients at increasing dose levels and observing toxic effects to determine the dose recommended for phase II study. Among 610 patients, 26% were treated at or within 10% of the recommended dose and 35% were treated with less than 50% of the recommended dose or on a trial that yielded no recommended dose. Among 18 trials using agents previously tested in humans, fewer patients were treated at much less than the recommended dose. For trials in which myelosuppression was dose-limiting, the estimated probability of serious myelosuppression associated with the recommended dose ranged from 23% to 66%. Nineteen patients (3%) responded to therapy.

CONCLUSION

This summary of phase I trials recently conducted at M.D. Anderson Cancer Center confirms the need for alternative methods, provides baseline information against which alternatively conducted trials can be compared, and demonstrates some practical clinical trial issues not generally considered when alternative methods are proposed.
Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients.
Authors: De Conno F , Groff L , Brunelli C , Zecca E , Ventafridda V , Ripamonti C
Published: February 2017

PURPOSE

The aims of this study were to describe the analgesia, side effects, and dosage and the causes of suspension of treatment in a large sample of advanced cancer patients with pain after treatment with oral methadone from 7 to 90 days.

PATIENTS AND METHODS

In a retrospective study, data collected for 196 advanced cancer outpatients with moderate to severe pain treated at 8-hour intervals with oral methadone in solution form from February 1993 to February 1995 were analyzed at baseline (time 0) and then at 7, 15, 30, 45, 60, and 90 days. The following parameters were assessed: Karnofsky Performance Status, intensity of pain (using the Integrated Pain Score [IPS], intensity of pain, insomnia, drowsiness, confusion, dry mouth, nausea, vomiting, constipation, and dyspnea (using the Therapy Impact Questionnaire [TIQ], mean daily dose of drug administered, and reasons for withdrawal from study. The period when pain was reduced by > or = 35% with respect to baseline was evaluated with the Palliation Index. The association of the degree of palliation of pain with the age of the patients, tumor site, analgesic treatment taken at baseline, and daily mean dose of methadone administered during the follow-up period was analyzed by means of the Kruskal-Wallis test.

RESULTS

A reduction in pain intensity with respect to baseline occurred at each analysis time, and in 55.1% of the patients the reduction during the follow-up period was > or = 35% according to the Palliation Index. The mean dose of oral methadone ranged from 14 mg at day 7 to 23.65 mg at day 90. There was an overall worsening of the other symptoms, but a high percentage of the patients reported an amelioration of insomnia with respect to baseline. There was a statistically significant association (P < .0001) between the Palliation Index and the analgesic therapy administered at baseline. Only 11.2% of the patients withdrew from the study due to analgesic inefficacy and 6.6% due to methadone-related side effects (10 patients with drowsiness and three with severe constipation.

CONCLUSION

Oral methadone administered every 8 hours was shown to be an appropriate analgesic therapy in the treatment of advanced cancer-related pain. The worsening of the other symptoms under study can be considered linked to the progression of the disease, and in fact, only a small percentage of the patients reported methadone-related side effects that warranted suspension of treatment. We consider oral methadone to be a useful analgesic therapy, and it should be considered in clinical practice for the treatment of cancer pain.
Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer.
Authors: Saarto T , Blomqvist C , Ehnholm C , Taskinen M R , Elomaa I
Published: February 2017

PURPOSE

To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen.

PATIENTS AND METHODS

Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy.

RESULTS

Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%).

CONCLUSION

These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.
High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.
Authors: Martelli M , Vignetti M , Zinzani P L , Gherlinzoni F , Meloni G , Fiacchini M , De Sanctis V , Papa G , Martelli M F , Calabresi F , Tura S , Mandelli F
Published: February 2017

PURPOSE

To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy.

PATIENTS AND METHODS

From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT.

RESULTS

The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group.

CONCLUSION

Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.
Chemotherapy in malignant pleural mesothelioma. A review.
Authors: Ong S T , Vogelzang N J
Published: February 2017

PURPOSE AND DESIGN

We reviewed the published literature of clinical studies in malignant pleural mesothelioma, including phase II trials of the newer antifolates and plant derivatives, as well as older single-agent and combination chemotherapy trials. We excluded trials with less than 15 patients, although we have mentioned smaller trials in the text to make a specific point, as well as ones that show promise. We have also included confidence intervals when cited in the original reports, or calculated them when absent.

RESULTS

No drugs have consistently induced a response greater than 20%. Higher response rates have been reported with detorubicin, high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively, but these have yet to be confirmed. Agents that produce response rates in 10% to 20% of patients include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination chemotherapy trials do not demonstrate a consistently greater response rate than single-agent trials. However, the combination of doxorubicin, cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44% (95% confidence interval, 27% to 63%), but this remains unconfirmed. Intrapleural therapy using interferon gamma, particularly for small-volume disease, shows promise.

CONCLUSION

The successful treatment of unresectable pleural mesothelioma awaits the discovery of active drugs. Recent trials of high-dose methotrexate and other antifolates are encouraging. Newer agents, including suramin, should be evaluated in phase II trials. Off-protocol combination therapy cannot be recommended over single-agent therapy, but studies that use combinations of the newer agents should be conducted.
Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil.
Authors: Findlay M , Young H , Cunningham D , Iveson A , Cronin B , Hickish T , Pratt B , Husband J , Flower M , Ott R
Published: February 2017

PURPOSE

To investigate and measure the metabolism of colorectal cancer liver metastases using 18F-fluorodeoxyglucose positron emission tomography (FDG PET), before and during the first month of chemotherapy. The findings were compared with tumor outcome conventionally assessed using changes in tumor size.

PATIENTS AND METHODS

Patients with colorectal cancer liver metastases were treated with fluorouracil (5FU) as a protracted venous infusion (300 mg/m2/d), with or without interferon-alpha 2b for two 10-week blocks separated by a 2-week break. Before and at 1 to 2 and 4 to 5 weeks on treatment, FDG PET scans were performed. Patients fasted, were injected intravenously with FDG (50 to 100 MBq), and scanned using a large-area positron camera; the image data was processed such that regions of interest could be identified. The results were expressed as a ratio of FDG uptake in the tumor and normal liver (T:L) or as a semiquantitative standardized uptake value (SUV). These measures were compared with the tumor dimensions measured on a computed tomographic (CT) scan performed at 12 weeks from commencement of chemotherapy.

RESULTS

Twenty patients were studied; however, two did not have assessable liver metastases. Objective partial responses were observed in 11 of 18 patients. A total of 27 metastatic lesions were assessable. Pretreatment T:L ratios and SUVs did not correlate with tumor response, although response was associated with lower 1- to 2-week (1.84 v 2.17; t=2.667; P < .02) and 4- to 5-week (1.36 v 2.28; t=5.02; P < .001) T:L ratios, and 4- to 5-week (3.57 v 4.95; t=2.492; P < .05) SUVs. Expressed as a percent of the baseline values of the T:L ratio, responding lesions had a greater reduction in metabolism (67% v 99%; t=7.53; P < .001). The 4- to 5-week T:L ratio was able to discriminate response from nonresponse both in a lesion-by-lesion and overall patient response assessment (sensitivity 100%; specificity 90% and 75%, respectively).

CONCLUSION

Positron emission tomography used to evaluate the uptake of FDG in tumors yields data that correlate with the antitumor effect of chemotherapy in patients with liver metastases from colorectal cancer.
Follow-up of Memorial Sloan-Kettering Cancer Center patients treated on National Cancer Institute Treatment Referral Center protocol 9103: paclitaxel in refractory ovarian cancer.
Authors: Markman M , Hakes T , Barakat R , Curtin J , Almadrones L , Hoskins W
Published: February 2017

PURPOSE

To examine the short-term and long-term results of paclitaxel therapy in patients with advanced heavily pretreated, cisplatin-refractory ovarian cancer.

PATIENTS AND METHODS

The results of treatment for patients entered onto National Cancer Institute (NCI) Treatment Referral Center protocol 9103 at the Memorial Sloan-Kettering Cancer Center (MSKCC) were reviewed to evaluate toxicity, efficacy, and survival.

RESULTS

Of 46 individuals with measurable disease treated on the protocol at MSKCC, the objective response rate was only 4%. However, the 2- and 3-year survival rates for all 103 patients (including both measurable and nonmeasurable populations) entered onto this study at MSKCC were 18% and 11%, respectively. Twenty-one percent of patients received > or = six courses of paclitaxel, which suggests treatment-related stabilization of disease may have had a greater impact on the natural history of the malignancy than indicated by the objective response rate.

CONCLUSION

This experience supports the hypothesis that a more prolonged delivery of paclitaxel (ie, > six courses), a cell-cycle-specific cytotoxic agent with limited or no cumulative toxicity, may result in an improved therapeutic outcome in ovarian cancer. This concept will need to be tested in a randomized phase 3 clinical trial.
Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.
Authors: Coindre J M , Terrier P , Bui N B , Bonichon F , Collin F , Le Doussal V , Mandard A M , Vilain M O , Jacquemier J , Duplay H , Sastre X , Barlier C , Henry-Amar M , Macé-Lesech J , Contesso G
Published: February 2017

PURPOSE

To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment.

PATIENTS AND METHODS

Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence.

RESULTS

Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy.

CONCLUSION

Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.
Primary non-Hodgkin's lymphoma of the CNS treated with BVAM or CHOD/BVAM chemotherapy before radiotherapy.
Authors: Bessell E M , Graus F , Punt J A , Firth J L , Hope D T , Moloney A J , Lopez-Guillermo A , Villa S
Published: February 2017

PURPOSE

To assess whether chemotherapy that includes drugs that cross the blood-brain barrier improves survival in primary CNS non-Hodgkin's lymphoma (PCNSL) when combined with radiotherapy.

PATIENTS AND METHODS

Thirty-four patients, with no evidence of human immunodeficiency virus type 1 (HIV-1) infection, were treated with the related chemotherapy regimens of carmustine (BCNU), vincristine, cytarabine, and methotrexate (BVAM; 12 patients), cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/BVAM (17 patients) and intensified CHOD/BVAM (five patients) between 1986 and 1994. The median age was 60 years (range, 16 to 73) and 47% had a performance status of 3 or 4 (Eastern Cooperative Oncology Group [ECOG]/World Health Organization [WHO]). Ten patients were treated with BVAM chemotherapy between 1986 and 1989, and subsequently 17 patients were treated with CHOD/BVAM (cytarabine 3 g/m2). Twenty of these 27 patients received whole-brain radiotherapy (craniospinal in four).

RESULTS

The complete response (CR) rate at the completion of chemotherapy was 63% for BVAM and 67% for CHOD/BVAM; more neutropenia occurred with CHOD/BVAM. The 5-year actuarial probability of survival of all 34 patients was 33% (95% confidence interval [CI], 14% to 52%), with so far only one recurrence after 2 years. Using multivariate analysis, age (P = .0005) and number of tumors at diagnosis (P = .0358) were prognostic factors. All five patients aged > or = 70 years died during or shortly after chemotherapy. Performance status was not an independent variable.

CONCLUSION

The BVAM or CHOD/BVAM regimens can be delivered despite neutropenia without significant treatment delay or dose reduction in patients less than 70 years of age. Further intensification of this type of chemotherapy is probably not possible with patients of this age, many of whom have a poor performance status.
Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients.
Authors: Zinzani P L , Bendandi M , Martelli M , Falini B , Sabattini E , Amadori S , Gherlinzoni F , Martelli M F , Mandelli F , Tura S , Pileri S A
Published: February 2017

PURPOSE

During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD).

PATIENTS AND METHODS

From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively.

RESULTS

Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms.

CONCLUSION

The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.
Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.
Authors: Hanks G E , Hanlon A L , Hudes G , Lee W R , Suasin W , Schultheiss T E
Published: February 2017

PURPOSE

The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments.

MATERIALS AND METHODS

One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm).

RESULTS

There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis.

CONCLUSION

Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.
Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients.
Authors: Dahut W , Harold N , Takimoto C , Allegra C , Chen A , Hamilton J M , Arbuck S , Sorensen M , Grollman F , Nakashima H , Lieberman R , Liang M , Corse W , Grem J
Published: February 2017

PURPOSE

To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC).

PATIENTS AND MATERIALS

A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF.

RESULTS

Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count < 25,000/microL in one). With G-CSF, zero of seven patients treated with 47 microg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/microL in five) entered at 59 microg/m2/h. Among 39 patients entered at > or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85).

CONCLUSION

The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.
Autologous peripheral-blood progenitor-cell support following high-dosechemotherapy or chemoradiotherapy in patients with high-risk multiple myeloma.
Authors: Marit G , Faberes C , Pico J L , Boiron J M , Bourhis J H , Brault P , Bernard P , Foures C , Cony-Makhoul P , Puntous M , Vezon G , Broustet A , Girault D , Reiffers J
Published: February 2017

PURPOSE

The aims of the current study were to evaluate in patients with high-risk multiple myeloma (MM) the feasibility and usefulness of high-dose chemotherapy or chemoradiotherapy followed by hematopoietic stem-cell support with autologous peripheral-blood progenitor cells (PBPC) harvested after high-dose cyclophosphamide (HDCYC).

PATIENTS AND METHODS

Seventy-three patients with high-risk MM were entered onto the study. Before the procedure, all patients had received HDCYC to collect PBPC by leukapheresis. One patient died of infection after HDCYC. All other patients subsequently received high-dose melphalan (HDM) (140 mg/m2) either alone (n = 1) or associated with either busulfan (16 mg/kg; n = 4) or total-body irradiation (TBI) (8 to 15 Gy; n= 67). In addition, three of the latter patients received cyclophosphamide (120 mg/kg). Thereafter, PBPC were reinfused either alone in 61 patients or together with back-up bone marrow cells in 11 patients in whom the granulocyte-macrophage colony-forming unit (CFU-GM) cell content of the leukapheresis was low.

RESULTS

One patient died of acute cardiac failure after reinfusion of PBPC; three patients did not respond after autologous blood progenitor cell transplantation (ABPCT), while the other 68 patients achieved either a complete response (CR; n = 32) or partial response (PR; n = 36). Thirty-six patients relapsed or progressed after a median response duration of 14.5 months (range, 3 to 43) and 19 of these subsequently died. Four other patients died while still responsive of lung cancer (n = 1) or infection (n = 3). The remaining 28 patients are currently alive and still responding with a median follow-up duration of 27 months (range, 6 to 66). The 3-year probability of survival was 66% +/- 12% (95% confidence interval [CI] after ABPCT and 77% +/- 51% (95% CI) from diagnosis.

CONCLUSION

High-dose chemotherapy or chemoradiotherapy followed by autologous PBPC support in MM is feasible and efficient. Further studies are needed to confirm these encouraging, although preliminary, results and to compare this technique with other therapeutic strategies.
Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation.
Authors: Sierra J , Brunet S , Grañena A , Olivé T , Bueno J , Ribera J M , Petit J , Besses C , Llorente A , Guardia R , Macía J , Rovira M , Badell I , Vela E , Díaz de Heredia C , Vivancos P , Carreras E , Feliu E , Montserrat E , Julía A , Cubells J , Rozman C , Domingo A , Ortega J J
Published: February 2017

PURPOSE

To evaluate prospectively the feasibility and results of bone marrow transplantation (BMT) after induction and intensification chemotherapy (CT) in patients with de novo acute myeloid leukemia (AML).

PATIENTS AND METHODS

A total of 159 patients less than 51 years of age were treated. Induction CT consisted of daunorubicin 60 mg/m2 for 3 days, cytarabine (ARA-C) 100mg/m2 for 7 days, and etoposide 100 mg/m2 for 3 days. The first intensification therapy included mitoxantrone 10 mg/m2 for 3 days and ARA-C 1.2 g/m2 every 12 hours for 4 days. Amsacrine (100 or 150 mg/m2 for 3 days) and ARA-C (1.2 g/m2 every 12 hours for 2 or 4 days) were given as the second intensification therapy. Depending on the availability of a human leukocyte antigen (HLA)-identical sibling, the intention of treatment after CT was allogeneic BMT (allo-BMT) or autologous BMT (ABMT).

RESULTS

Complete remission (CR) was obtained in 120 patients (75%) and partial remission (PR) in 11 (7%), while 15 patients (10%) were refractory and 13 (8%) died during induction. There was a trend for better leukemia-free survival (LFS) at 4 years for patients assigned to the ABMT group (50% +/- 6%) compared with the allo-BMT group (31% +/- 7%) (P = .08). This difference in LFS reached statistical significance when considering only transplanted patients (63% +/- 3% at 4 years after ABMT and 38% +/- 11% after allo-BMT, P = .02). The favorable results in patients who received ABMT (no toxic deaths and 37% +/- 7% probability of relapse at 4 years) contrast with the poor outcome of allografted patients (11 patients with transplant-related mortality).

CONCLUSION

Our study reflects the difficulties in the completion of a therapeutic strategy that include BMT and suggests that intensification before BMT may be useful in the setting of ABMT, but this approach was associated with a high mortality rate in allo-BMT patients.
Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer.
Authors: Greco F A , Stroup S L , Gray J R , Hainsworth J D
Published: February 2017

PURPOSE

The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients.

PATIENTS AND METHODS

Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10.

RESULTS

This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached.

CONCLUSION

This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.
CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.
Authors: Alcorn M J , Holyoake T L , Richmond L , Pearson C , Farrell E , Kyle B , Dunlop D J , Fitzsimons E , Steward W P , Pragnell I B , Franklin I M
Published: February 2017

PURPOSE

The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy.

PATIENTS AND METHODS

For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin.

RESULTS

The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls.

CONCLUSION

These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.
Diffuse Small Noncleaved-Cell, Non-Burkitt's Lymphoma in Adults
Authors: Longo Don L. , Duffey Patricia L. , Jaffe Elaine S. , Raffeld Mark , Hubbard Susan M. , Fisher Richard I. , Wittes Robert E. , DeVita Vincent T. , Young Robert C.
Published: February 2017

A 1994 report by Longo et al, entitled "Diffuse Small Noncleaved-Cell, Non-Burkitt's Lymphoma in Adults: A High-Grade Lymphoma Responsive to ProMACE-Based Combination Chemotherapy" (J Clin Oncol 12:2153–2159) contained an error. In the Patients and Methods section, on page 2155, line 6 of the left column should have read: ". ...bleomycin 5U/m day 8, methotrexate 120 mg/m2 on day 8... ."
Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer.
Authors: Kemp G , Rose P , Lurain J , Berman M , Manetta A , Roullet B , Homesley H , Belpomme D , Glick J
Published: February 2017

PURPOSE

Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer.

PATIENTS AND METHODS

Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival.

RESULTS

Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), > or = 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the principal side effects were emesis and a transient decrease in blood pressure.

CONCLUSION

Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.
Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study.
Authors: Kramer M H , Hermans J , Parker J , Krol A D , Kluin-Nelemans J C , Haak H L , van Groningen K , van Krieken J H , de Jong D , Kluin P M
Published: February 2017

PURPOSE

We studied the prognostic significance of bcl2 and p53 protein expression in relation to clinical and pathologic characteristics in patients with diffuse large B-cell lymphoma (LCL).

PATIENTS AND METHODS

Three hundred seventy-two patients with LCL were retrieved from a population-based registry for non-Hodgkin's lymphoma (NHL). bcl2 and p53 protein expression was studied on paraffin-embedded tumor tissue by immunohistochemistry in relation to clinical factors. Response to therapy and survival were analyzed in 165 patients who were uniformly staged and treated and for whom all prognostic data were available according to the International Prognostic Index (IPI).

RESULTS

Forty-five percent of tumors showed strong expression of the bcl2 protein (bcl2++), with a higher frequency in patients with primary nodal involvement. Disease-free survival (DFS) was significantly better in bcl2-negative/intermediate (bcl2-/+) cases as compared with bcl2++ cases (P = .0011). At 5 years, bcl2-/+ patients showed a DFS rate of 74%, in contrast to bcl2++ patients with a DFS rate of 41% (P = .002). Bcl2 was the strongest independent prognostic value in a multivariate analysis, with a relative risk (RR) of 3.0 in comparison to p53 expression and the clinical factors of the IPI. Overall survival (OS) was not significantly influenced by bcl2 protein expression. p53 protein expression was found in 13% of cases, with a higher frequency in patients with extensive disease. p53 expression did not influence the chance to achieve complete remission (CR) and survival.

CONCLUSION

bcl2 protein is frequently expressed in LCL and is a strong independent prognostic factor for DFS. p53 expression is related with high tumor burden, but is not an independent risk factor for CR and survival.
Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.
Authors: Bladé J , San Miguel J F , Fontanillas M , Alcalá A , Maldonado J , García-Conde J , Conde E , Conzález-Brito G , Moro M J , Escudero M L , Trujillo J , Pascual A , Rozman C , Estapé J , Montserrat E
Published: February 2017

PURPOSE

To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy.

PATIENTS AND METHODS

From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report.

RESULTS

Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis.

CONCLUSION

The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.
Challenges and opportunities of the Internet for medical oncology.
Authors: Glodé L M
Published: February 2017

PURPOSE

The internet, and in particular the world wide web (www), has a rapidly increasing potential to provide information for oncologists and their patients about cancer biology and treatment. A brief overview of this environment is given along with examples of how easily the information is accessed as a means of introducing the web page of the American Society of Clinical Oncology (ASCO), ASCO OnLine.

METHODS

Oncology information sources on the www were accessed from the author's home using a 14.4 kbs modem, Netscape browser (Netscape communications Corp, Mountain View, CA), and the locations recorded for tabulation and discussion.

RESULTS

Overwhelming amounts of oncology-related information are now available via the Internet.

CONCLUSION

Oncology as a subspecialty is ideally suited to apply the newest information technology to traditional needs in areas of education, research, and patient care. Oncologists will increasingly act as information guides rather than information resources for patients and their families with cancer.