bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of advanced neuroblastoma with supralethal chemotherapy, radiation, and allogeneic or autologous marrow reconstitution.
Authors: August C S , Serota F T , Koch P A , Burkey E , Schlesinger H , Elkins W L , Evans A E , D'Angio G J
Published: February 2017

Ten children with recurrent metastatic (stage IV) neuroblastoma received local radiation therapy, supralethal chemotherapy, and total-body irradiation. Rescue with infusions of either allogeneic (four patients) or autologous (six patients) bone marrow followed. The drugs given to the first two patients were individualized combinations based on previous tumor responses. Both patients died with recurrent tumor three and nine months posttransplant. The eight remaining patients were treated more uniformly with local irradiation, VM-26, doxorubicin, melphalan (L-phenylalanine mustard), and 1,000-rad total-body irradiation in three fractions. Two of these patients had cardiac dysfunction and received no doxorubicin. Three children died in the immediate posttransplant period with disseminated fungal infections. A fourth relapsed and died nine months posttransplant. As of December 1, 1983, two children who received allogeneic marrow grafts have survived in complete remission for 54 and 36 months, and two children who received autologous marrow grafts have survived in complete remission for 35 and 22 months. These results suggest that relapsed metastatic neuroblastoma can be controlled by supralethal combinations of chemotherapy and irradiation coupled with bone-marrow rescue.
Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study.
Authors: Winkler K , Beron G , Kotz R , Salzer-Kuntschik M , Beck J , Beck W , Brandeis W , Ebell W , Erttmann R , Göbel U
Published: February 2017

From December 1979 to August 1982 158 patients were registered for an adjuvant chemotherapy (CT) study COSS -80. To compare the effect of cisplatin (CPL) to that of the drug combination bleomycin, cyclophosphamide, and dactinomycin (BCD), patients were randomized to receive either drug(s) within a course of sequential multidrug CT including doxorubicin and high-dose methotrexate (HDMTX). Definite surgery was done 10-18 weeks after the start of CT. Patients were randomized a second time to receive or not to receive fibroblast interferon in addition to CT beginning at week 16. At a median observation time of 19.5 months (range, 4-34 months), 116 (73%) of 158 patients were continuously disease-free (CDF). After exclusion of 42 patients because of some deviation in history and/or management, 86 (74%) of 116 patients actually were CDF with a 30-month calculated CDF-rate of 68%. There was no difference in CDF rates in the patients receiving BCD versus CPL or receiving interferon versus no interferon. Whereas, in comparison to the previous study COSS -77, the over-all increase in CDF rate does not reach statistical significance, it does, however, for the younger (less than or equal to 12 years) and for male patients, which is assumed to be the effect of increasing the methotrexate dose from 6 to 12 g/m2 in the COSS -80 study.
An approach to conducting epidemiologic research within cooperative clinical trials groups.
Authors: Grufferman S , Delzell E , Delong E R
Published: February 2017

Cooperative clinical trials groups offer exciting opportunities for conducting epidemiologic research for several reasons: they facilitate accrual of sufficient numbers of subjects in a short period of time, even for studies of rare diseases; they provide uniform pathologic review and uniform collection of subjects' entry data; and they provide a more representative sample of cases than a single-institution study. Despite these advantages, few epidemiologic studies of etiologic factors have been done through these groups because methods for selecting appropriate control subjects and for obtaining information from geographically scattered subjects have not been available. An approach that can serve as a model for this type of research has been developed. A collaborative case-control study of childhood rhabdomyosarcoma (RMS) with the Intergroup Rhabdomyosarcoma Study (IRS) was recently begun. The study, which is independently funded, evaluates the role of environmental factors in the etiology of RMS. Parents of subjects were interviewed by telephone and control subjects were selected from the same communities as patients by random digit dialing . Interview data are supplemented by information from birth certificates and, for patients, by IRS data. This new methodology permits a large study of a rare tumor in a relatively short period of time.
A randomized trial of melphalan and prednisone versus melphalan, prednisone, cyclophosphamide, MeCCNU, and vincristine in untreated multiple myeloma.
Authors: Pavlovsky S , Saslavsky J , Tezanos Pinto M , Palmer L , Curuchet M , Lein J M , Garay G , Dragosky M , Quiroga-Micheo E , Huberman A B
Published: February 2017

In a randomized study with 234 previously untreated patients with multiple myeloma, 129 were treated with melphalan (8 mg/m2 perorally for four days) and prednisone (40 mg/m2 perorally for seven days, both every four weeks) and 105 with melphalan and prednisone at the same doses plus cyclophosphamide (600 mg/m2 intravenously every four weeks), MeCCNU (100 mg/m2 PO every eight weeks), and vincristine (MPCCV, 0.6 mg/m2 IV every four weeks). A total of 49 (38%) of the 129 patients treated with melphalan and prednisone (MP) and 48 (46%) of the 105 patients treated with MPCCV showed good response (GR) (P not significant); the overall response rates were 58% and 70%, respectively. Thirty-seven percent of the MP group and 39% of the MPCCV group remain alive at 48 months from first treatment (P not significant). The estimated 48-month survival from first treatment, according to different prognostic factors at diagnosis, in both groups was as follows: stage 1,56%; stage II, 46%, and stage III, 23% (I and II v III P less than .001). Survival at 48 months according to response was GR, 68%; partial response (PR), 33%; and null, 16% (GR v null, P less than .0005; GR v PR, P less than .0005). Survival according to renal function was 43% for a creatinine level less than 2 mg/100 mL and 27% for a creatine level greater than or equal to 2 mg/100 mL (P less than .0005). No significant difference has been found between the two treatment schedules in terms of response rate and survival time, in any stage of disease.
Informed consent for investigational chemotherapy: patients' and physicians' perceptions.
Authors: Penman D T , Holland J C , Bahna G F , Morrow G , Schmale A H , Derogatis L R , Carnrike C L , Cherry R
Published: February 2017

One hundred forty-four patients and 68 physicians at three cancer centers were studied for their perceptions of the consent procedure, in which they participated one to three weeks earlier, for chemotherapy by one of 65 investigational protocols. Patients recalled the procedure positively and relied heavily on physician's advice. They felt most physicians wanted them to accept; 29% felt their participation in the decision was not encouraged. Primary reasons for accepting were trust in the physician, belief the treatment would help, and fear the disease (viewed as highly serious) would get worse without it. Nearly a fourth did not recall the information given that treatment was investigational. The consent form played no role in decision-making for 69%. Physicians believed therapeutic benefits would exceed potential problems for most patients; they viewed 41% of the patients as less than eager for details of treatment, a third as avoiding the seriousness of the discussion, and a third as passive in decision-making. The perceptual set of both parties places inadvertent constraint on patients' autonomy in decision making.
Paradoxical effects of prophylactic phenothiazine antiemetics in children receiving chemotherapy.
Authors: Zeltzer L , LeBaron S , Zeltzer P M
Published: February 2017

The effectiveness of prophylactic phenothiazine antiemetics on reduction of nausea and vomiting was assessed for 23 children (age, 9-17 years) who had intermittently received antiemetics (ie, for one course but not for another). Each patient was his own control and the courses with antiemetics were compared to the matched courses without antiemetics (Wilcoxon matched-pairs, signed-ranks test). In each case, the matched courses with and without antiemetics were temporally consecutive and equivalent for chemotherapeutic agents and dosages. Significantly higher ratings for severity of nausea (P less than .004), vomiting (P less than .02), and the extent to which these symptoms bothered patients (P less than .001) were found during courses with prophylactic antiemetics. Duration (in hours) of nausea and vomiting was analyzed for the last eight consecutive study patients; in eight of eight patients, a significantly longer duration of nausea (P less than .05) and vomiting (P less than .02) was found for the courses in which antiemetics were given prophylactically. This study suggests that prophylactic phenothiazine antiemetics do not predictably reduce children's nausea and vomiting and may even be associated with an increase in symptoms. Further studies in children are needed to determine which patients might benefit most from antiemetic intervention.
Pathologic findings at orchiectomy following chemotherapy for disseminated testicular cancer.
Authors: Greist A , Einhorn L H , Williams S D , Donohue J P , Rowland R G
Published: February 2017

Patients with testicular cancer who have disseminated disease at presentation do not always undergo orchiectomy for diagnosis of staging before initiation of chemotherapy. Between October 1978 and November 1982 orchiectomy was performed following cisplatin combination chemotherapy in 20 patients with disseminated germ cell tumors. There were three patients with residual carcinoma in the removed testis and six patients with teratoma. Therefore, in patients with evidence of a primary testicular neoplasm that was not resected initially, orchiectomy should be performed after chemotherapy. Furthermore, the testis may be a sanctuary site for germ cell malignancies during systemic treatment.
Phase I trial of esorubicin (4'deoxydoxorubicin).
Authors: Garewal H S , Robertone A , Salmon S E , Jones S E , Alberts D S , Brooks R
Published: February 2017

A phase I study of 4'deoxydoxorubicin (esorubicin) was performed on an every-21-day bolus intravenous (IV) schedule in 36 patients with advanced cancer. Thirty-four patients were evaluable for toxicity analysis. Toxicity included mild nausea, occasional local skin reactions, and mild to moderate alopecia. Myelo-suppression was dose limiting. Clinically evident congestive heart failure was not observed. However, two patients developed premature ventricular contractions. Overall, esorubicin was better tolerated than doxorubicin at equally potent doses. Although response analysis was not the primary objective of this phase I study, minor responses were observed in melanoma, breast cancer, lymphoma, and gastric cancer. On the basis of this study, a starting dose of 30 mg/m2 IV every 21 days is recommended for good-risk patients with escalation to 32.5 mg/m2 depending on bone marrow tolerance. For patients with poor bone marrow reserve, a starting dose of 25 mg/m2 every 21 days is recommended. Phase II trials with esorubicin in this dosage schedule are clearly warranted in a wide variety of metastatic neoplasms including a substantial population of patients who have not received prior chemotherapy.
High-dose polychemotherapy with autologous bone marrow transplantation in children with relapsed lymphomas.
Authors: Hartmann O , Pein F , Beaujean F , Kalifa C , Patte C , Parmentier C , Lemerle J
Published: February 2017

Sixteen children with non-Hodgkin's lymphoma (NHL) who had relapsed were treated with high-dose chemotherapy with BCNU, cyclophosphamide, cytarabine, 6-thioguanine (high-dose chemotherapy [HDC]) and autologous bone marrow transplantation (ABMT). Eleven complete responses were obtained and five patients remain in prolonged complete unmaintained remission 77+ to 152+ weeks after treatment. The best results were obtained in patients with CNS involvement and when this regimen was used after complete remission or partial response was obtained by other means. The results appear to be better in B-cell than in T-cell lymphomas, but the numbers are too small for statistical assessment. The use of ABMT rendered the pancytopenic period short and safe, despite the use of drug doses higher than those previously described for this HDC. The frequency of interstitial pneumonitis, possibly related to pulmonary toxicity of chemotherapy, remains a major concern. These results show that this regimen can help to cure some patients but its toxicity prohibits its use in primary therapy.
Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.
Authors: Lenhard R E , Order S E , Spunberg J J , Asbell S O , Leibel S A
Published: February 2017

Thirty-eight patients with advanced, progressive Hodgkin's disease who had relapsed from or who had not responded to treatment with at least two potentially curative combination chemotherapy regimens were entered into this phase 2 study. All patients received 131I antiferritin antibody administered intravenously (IV) at a dose of 30 mCi on day 0 and 20 mCi on day 5. Antibody was derived from rabbit, pig, and monkey species. Objective partial remission of measurable disease was recorded in 40% of patients. Symptomatic response was recorded in 77% of patients. Toxicity was restricted to bone marrow depression with thrombocytopenia greater than leukopenia. These responses are comparable to other reported phase 2 drugs in this patient population and subsequent trials of antibody free of radioactivity and antibody using a beta emitting isotope are being carried out to expand upon these results.
Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma.
Authors: Sekine H , Hayes D F , Ohno T , Keefe K A , Schaetzl E , Bast R C , Knapp R , Kufe D W
Published: February 2017

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.
Clinical pharmacokinetics of high-dose metoclopramide in cancer patients receiving cisplatin therapy.
Authors: McDermed J E , Cohen J L , Joseph C , Strum S B
Published: February 2017

Using a sensitive and specific high-pressure liquid chromatographic (HPLC) assay, we measured serum levels of metoclopramide in 18 cancer patients receiving high-dose intravenous (IV) therapy to prevent cisplatin-induced emesis. Ten patients were treated with one or more courses with metoclopramide alone (1.0 to 3.0 mg/kg) in an open-label study, and eight patients were treated with a fixed 2.0 mg/kg dose of metoclopramide with or without adjunct dexamethasone (20 mg) using a randomized, crossover design. The pharmacokinetics of metoclopramide were determined, and the relationship between serum levels and clinical response was evaluated. The pharmacokinetic parameters of high-dose metoclopramide were found to be similar to those reported for standard promotility doses, and no dose dependency was demonstrated over the range of doses studied. No clear correlation between serum metoclopramide levels and prevention of cisplatin-induced emesis was observed. The addition of dexamethasone resulted in clinical improvement in two of eight patients, but had no effect on serum metoclopramide levels or kinetic parameters. Results in this study population do not show metoclopramide levels to be related to antiemetic effect following IV cisplatin therapy.
Improvements in data collection through physician use of a computer-based chemotherapy treatment consultant.
Authors: Kent D L , Shortliffe E H , Carlson R W , Bischoff M B , Jacobs C D
Published: February 2017

The impact of a computer-based data management system on the completeness of clinical trial data was studied before and after the system's introduction in an oncology clinic. Physicians use the system, termed ONCOCIN, to record data during patient visits and to receive advice about treatment and tests required by experimental cancer protocols. Although ONCOCIN does not force the user to enter all data expected by the protocol, after its introduction there was improvement in the recording frequency of such data. The percentage of expected physical findings recorded increased from 74% to 91% (P less than .05), toxicity history from less than 1% to 45% (P less than .01), general chemistry results from 36% to 82% (P less than .01), x-ray results from 44% to 73% (P less than .01), and physicians' assessments of overall disease activity and Karnofsky performance status from 73% to 91% (P less than .05). Analysis of the steps in data collection and their contribution to loss of data suggests that observations or test ordering which are dependent on the physician are most improved by the system. Furthermore, analysis of post-ONCOCIN visits when the system was unavailable suggests that the recording of physician-dependent data (physical findings and assessments of disease activity and performance status) is likely to revert to pre-ONCOCIN levels if the system is not used routinely. The results show that ONCOCIN can greatly enhance recovery of those data expected for chemotherapy protocol patients. The program's interaction with the physician is central to its effectiveness in data collection, especially for data that arise directly from the patient-physician encounter.
Exploratory data analysis and the use of the hazard function for interpreting survival data: an investigator's primer.
Authors: Simes R J , Zelen M
Published: February 2017

This report discusses how one can use the hazard function to gain important insights on the patterns of failure in clinical studies when the principal endpoint is a time metric. These new insights may help gain increased understanding into the pathogenesis of a chronic disease and how it is affected by treatment intervention. The qualitative behavior of the hazard function can reveal whether mortality is increasing, decreasing, or is constant over time. Simple graphic plots are all that is necessary to show characteristic failure patterns. These informal procedures are in the spirit of carrying out exploratory analyses on the data. This report discusses the organization of clinical data using a "branch and leaf" plot, outlines the calculation of the hazard function and life table, and uses examples from lung cancer and uveal melanoma to illustrate calculations and ways of interpreting hazard functions.
VP-16 and cisplatin as first-line therapy for small-cell lung cancer.
Authors: Evans W K , Shepherd F A , Feld R , Osoba D , Dang P , Deboer G
Published: February 2017

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.
Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group.
Authors: Büchner T , Urbanitz D , Hiddemann W , Rühl H , Ludwig W D , Fischer J , Aul H C , Vaupel H A , Kuse R , Zeile G
Published: February 2017

In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.
Differing complications of hyperleukocytosis in children with acute lymphoblastic or acute nonlymphoblastic leukemia.
Authors: Bunin N J , Pui C H
Published: February 2017

We assessed the frequency and outcome of complications associated with hyperleukocytosis in children who had received remission induction therapy for either acute lymphoblastic leukemia (ALL) or acute nonlymphoblastic leukemia (ANLL). Among 234 consecutive patients with a leukocyte count of 100 X 10(9)/L or greater at diagnosis, the frequency of early death was significantly higher in those with ANLL (23% v 5% for patients with ALL, P less than .001). The risk of early death increased with increasing leukocyte count, especially when it exceeded 300 X 10(9)/L in patients with ANLL (P less than .001). Intracerebral hemorrhage occurred in eight (11%) of the ANLL patients and accounted for six of the 17 early deaths; in all but two instances, the complication was associated with coagulopathy. Respiratory failure, presumably from pulmonary leukostasis, resulted in six other early deaths in ANLL patients. By contrast, intracerebral hemorrhage occurred in only two of the ALL patients (1.2%); both had normal coagulation studies, but leukocyte counts greater than 400 X 10(9)/L. Severe metabolic derangements from blast cell lysis accounted for three of the eight early deaths among patients with ALL. Leukapheresis or exchange transfusion effectively lowered the leukocyte counts of all 15 patients who received the procedures. Either method may be preferable to emergency cranial irradiation for preventing the complications of hyperleukocytosis in children with acute leukemia.
A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.
Authors: Buroker T R , Moertel C G , Fleming T R , Everson L K , Cullinan S A , Krook J E , Mailliard J A , Marschke R F , Klaassen D J , Laurie J A
Published: February 2017

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.
Prophylaxis of oropharyngeal candidiasis with clotrimazole.
Authors: Yeo E , Alvarado T , Fainstein V , Bodey G P
Published: February 2017

A total of 202 evaluable cancer patients were randomly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization. Oropharyngeal candidiasis occurred in 1% of the former patients and 27% of the latter patients (P less than .00001). Candida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis. Oropharyngeal candidiasis subsequently developed in 2% of the former patients and 38% of the latter patients (P = less than .00001). Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients.
Megestrol acetate therapy for advanced breast cancer.
Authors: Gregory E J , Cohen S C , Oines D W , Mims C H
Published: February 2017

One hundred twenty-four patients with metastatic breast cancer were treated with 40 mg of megestrol acetate four times daily. Complete responses (CR) or partial responses (PR) were seen in 29 patients (23%). CR, PR, or stable disease (S) was seen in 80 patients (65%). The median duration of response was 22 months for CR and PR and ten months for S. A significantly higher response rate (CR + PR) was seen in estrogen-receptor-positive (ER-positive) patients (26%) and in patients who had not received prior therapy (39%). A significant relationship to response could not be established for menopausal status, progesterone-receptor (PrR) status, dominant site of disease, or prior administration of chemotherapy. Median survival was 66+ months for responders, 35 months for patients with stable disease, and 9 months for nonresponders. These differences are all statistically significant (P less than .001). Toxicity was minimal, and side effects consisted primarily of weight gain, which was seen in 18 patients (14.5%). Megestrol acetate can provide effective palliation in patients with advanced breast cancer.
Intensive combination chemotherapy (ROAP 10) and splenectomy in the management of chronic myelogenous leukemia.
Authors: Kantarjian H M , Vellekoop L , McCredie K B , Keating M J , Hester J , Smith T , Barlogie B , Trujillo J , Freireich E J
Published: February 2017

To investigate the role of intensive chemotherapy in chronic myelogenous leukemia (CML), we treated 37 patients who had Philadelphia-positive benign-phase disease with rubidazone 300 mg/m2/d 1 (or daunorubicin 30 mg/m2/d X 4), cytosine arabinoside 80 mg/m2/d X 10, vincristine 2 mg/d 1, and prednisone 100 mg/d X 5 (ROAP 10), every four weeks for a median of three cycles. This treatment was followed by splenectomy and by subsequent maintenance therapy with 1 to 5 g hydroxyurea daily in intermittent courses. After a median follow-up of 42 months (range, 24 to 54 months), 20 patients (54%) remain in benign phase. The projected median survival is 52 months, and the three-year survival rate is 67%. Six patients (16%) developed blastic crisis, and eight died in the benign phase. A significant cytogenetic response, defined as a fall in the percentage of Philadelphia-positive cells to less than or equal to 30%, occurred in 18 (53%) of 34 patients who had serial cytogenetic studies. Six patients (18%) had reductions to 35% to 90%, whereas ten remained 100% positive. Cytogenetic response lasted for a median of six months from the time of maximal response (range, 1 to 18 months). Blastic crisis or accelerated disease developed in seven (44%) of the 16 patients who manifested minimal or no cytogenetic response, compared to only two of the 18 patients (11%) who achieved a significant cytogenetic response. Toxicity, which resulted in one death, was due to myelosuppression and consisted of febrile episodes during neutropenia (24% of courses), documented infections (8% of courses), and bleeding (8% of courses). ROAP 10 intensive therapy produces moderate survival improvement for CML patients compared to a matched historical control group of patients treated at our institution, but it has considerable myelosuppressive toxicity. The Philadelphia chromosome response is an important treatment-related prognostic factor.
Acute effects of salmon calcitonin in multiple myeloma: a valuable method for serial evaluation of osteoclastic lesions and disease activity--a prospective study of 125 patients.
Authors: Bataille R , Legendre C , Sany J
Published: February 2017

Hypocalcemia induced by salmon calcitonin (SCT) was evaluated in 125 patients with multiple myeloma (MM) and compared with 20 normal individuals (NCs) and 20 individuals with monoclonal gammopathy of undetermined significance (MGUS). It is now well documented that the maximum hypocalcemia (M delta CA) induced in man by SCT is related to the prevailing rate of osteoclastic resorption. In patients with MGUS, the level of M delta CA was normal. Conversely, the M delta CA was significantly abnormal in patients with MM (P less than .0001 for differences between NC/MGUS patients) and was correlated with (1) initial calcium levels (P less than .001), (2) the extent of lytic bone lesions (LBLs) (P less than .01), and (3) the myeloma cell mass (P less than .001) plus disease activity. The M delta CA was found to be of predictive value for new LBLs with or without hypercalcemia and to have dramatic influence on the survival of patients with MM. We conclude that the SCT-induced hypocalcemia test is of significant importance in the evaluation of the instantaneous rate of bone resorption and in the prognosis of patients with MM.
Chemotherapy of extragonadal germ cell tumors.
Authors: Logothetis C J , Samuels M L , Selig D E , Dexeus F H , Johnson D E , Swanson D A , von Eschenbach A C
Published: February 2017

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.
Improved survival with cyclic chemotherapy for nonseminomatous germ cell tumors of the testis.
Authors: Logothetis C J , Samuels M L , Selig D , Swanson D , Johnson D E , von Eschenbach A C
Published: February 2017

Forty-eight patients with advanced nonseminomatous germ cell tumors of the testis received a combination of cyclophosphamide, doxorubicin, and cisplatin (CISCAII) and a modified combination of vinblastine and bleomycin (VBIV) cyclic chemotherapy. Forty-four (92%) have achieved a complete remission. No patient in complete remission has relapsed with a mean follow-up of 139.0 weeks (SEM 7.0 weeks). The patients were stratified according to the modified Samuels clinical staging criteria. Thirty-seven (77%) had advanced disease (stage III-B3 to III-B5), ten of whom had advanced visceral non-lung disease (stage III-B5). Chemotherapy was individualized by tumor volume and response to therapy. Two courses were delivered after complete remission or the development of a stable mass with negative serum biomarkers. Twenty-four patients (50%) were explored for a persistent and stable mass. No viable cancer was found; 15 (62%) had mature teratomas and nine (38%) had scar. No patients suffered from doxorubicin cardiotoxicity, clinical pulmonary bleomycin toxicity, or persistent cisplatin renal failure. Four patients died. One patient, an unrecognized drug abuser, died of toxicity. Three with far-advanced tumors died of progressive disease. CISCAII/VBIV cyclic chemotherapy is superior to chemotherapy with vinblastine, bleomycin, and cisplatin, resulting in a 92% complete remission rate and a significant reduction in long-term toxicity.
Neoplasia and the erythron.
Authors: Doll D C , Weiss R B
Published: February 2017

Neoplasms may affect the erythroid system in a variety of ways. By far the most common abnormality associated with neoplastic disorders is anemia. It is important to recognize that there are multiple causes of anemia associated with neoplasms, because therapy of the anemia varies according to the causative mechanism. Less commonly, the paraneoplastic syndrome of erythrocytosis may occur in some patients with neoplasia. More subtle abnormalities of the erythrocytes associated with malignant disease include modification of the RBC membrane, changes in erythrocyte enzymes, and abnormalities in hemoglobin production. Clinical awareness of the multiple effects of neoplasms on the erythron will lead to better patient management and may also improve our understanding of erythropoiesis.
Second malignant neoplasms in children: an update from the Late Effects Study Group.
Authors: Meadows A T , Baum E , Fossati-Bellani F , Green D , Jenkin R D , Marsden B , Nesbit M , Newton W , Oberlin O , Sallan S G
Published: February 2017

This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.
Comparative activity and toxicity of cis-diamminedichloroplatinum (DDP) and a combination of doxorubicin, cyclophosphamide, and DDP in disseminated transitional cell carcinomas of the urinary tract.
Authors: Khandekar J D , Elson P J , DeWys W D , Slayton R E , Harris D T
Published: February 2017

From October 1978 to October 1981, 135 patients with disseminated transitional cell carcinomas of the urinary tract, with either measurable or evaluable disease, were randomized to receive either cis-diamminedichloroplatinum (DDP) or cyclophosphamide (CTX), Adriamycin (ADR) (Adria Laboratories, Columbus, Ohio), and DDP (CAD). DDP was given at a dose of 60 mg/m2, CTX at 400 mg/m2, and ADR at 40 mg/m2 intravenously every three weeks. Patients over the age of 65 and those with prior radiation received 75% of the dose initially. The dose was escalated if only mild toxicity developed. Of the patients on the CAD arm, 34% developed grade 3 or 4 hematologic toxicity, as compared to 3% in patients on the DDP therapy. Of the 93 patients with measurable disease, 48 received DDP. Seventeen percent had a partial or complete remission, as compared to 33% of the 45 patients on the CAD arm (P = .09). The crude median survival of patients on DDP was 6.0 months as compared to 7.3 months in patients receiving CAD (P = .17). We conclude that the CAD combination is more toxic than DDP with, at best, very marginal benefit in survival.
Cytosine-arabinoside-induced colitis and peritonitis: nonoperative management.
Authors: Johnson H , Smith T J , Desforges J
Published: February 2017

Cytosine arabinoside is known to cause severe gastrointestinal side effects in an already very ill patient population. Three cases are reviewed in which apparent surgical peritonitis was managed conservatively, with very careful clinical monitoring. Two of the patients recovered completely, and one died of systemic fungal infection. No patient had a surgically remediable condition, and all were extremely poor surgical risks. A review of our experience and the literature leads us to recommend careful conservative management in patients receiving cytosine arabinoside who appear to have a "surgical abdomen," but in whom a definitive surgical diagnosis cannot be made.
A randomized trial of adjuvant chemotherapy in head and neck cancer.
Authors: Taylor S G , Applebaum E , Showel J L , Norusis M , Holinger L D , Hutchinson J C , Murthy A K , Caldarelli D D
Published: February 2017

Ninety-five patients with squamous cell carcinoma of the head and neck were entered into a randomized study testing a two-week course of induction chemotherapy with methotrexate and leucovorin given prior to regional therapy. In addition, following regional therapy, patients randomized to chemotherapy were to receive similar methotrexate courses every three months for one year. Poor tolerance to this regimen after radiation and surgery led to a change in the chemotherapy following regional therapy to a combination of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin every three weeks for four cycles after the first 35 patients had been entered. Nine cases were ineligible and four lacked any follow-up data, leaving 82 analyzable cases. Using Cox regression analysis, no differences in the percentage of patients achieving disease control, the relapse-free survival, or the overall survival were identified between any treatment group. As has been described in many pilot studies of induction chemotherapy of head and neck cancer, chemotherapy responders had a more favorable disease-free survival than chemotherapy nonresponders in the total group of patients receiving adjuvant chemotherapy. However, correcting for imbalances in the expected three year disease-free survival of these patients, based on their disease site and stage, erased this difference, indicating tumor response to this regimen of chemotherapy is not an independent factor affecting disease outcome. The division of patients into arbitrary prognostic categories based on the expected outcome for each specific tumor site and stage proved to be a useful method for balancing treatment groups, given the multiple site-stage combinations within the upper aerodigestive tract. The defined prognostic categories were the single most sensitive predictors of relapse-free and overall survival.
Complications and management of implanted venous access catheters.
Authors: Lokich J J , Bothe A , Benotti P , Moore C
Published: February 2017

A totally implanted subclavian venous access system composed of a reservoir and silastic catheter was employed in 92 patients receiving infusion chemotherapy and/or hyperalimentation. The major catheter complication was subclavian or jugular vein thrombosis observed in 15 patients (16%). Thrombosis was observed in the ipsilateral subclavian or jugular vein surrounding the catheter without restricting function, except in two patients with thrombosis in the vein at the end of the catheter. Prophylaxis with low-dose Coumadin was effective in preventing thrombosis in high-risk patients as defined by a history of prior thrombosis. Streptokinase and/or heparin relieved the signs and symptoms of thrombosis, but clot dissolution or reversal of collateral flow was not observed. Explantation of the catheter was not necessary in all patients in that embolic complications of the thrombosis were not observed, and the system was retained and functioned in five patients in spite of the presence of thrombosis around the catheter. Other complications of the implanted system include "pocket" infection, catheter migration, and occlusion. Most complications may be managed without obligate catheter removal.
Immunogenicity of hepatitis B vaccine in oncology patients receiving chemotherapy.
Authors: Weitberg A B , Weitzman S A , Watkins E , Hinkle C , O'Rourke S , Dienstag J L
Published: February 2017

We evaluated the immunogenicity and safety of three 40 micrograms doses of hepatitis B vaccine in oncology patients receiving chemotherapy. Of 76 patients screened for entry into the study, 13 (17%) already had been exposed to hepatitis B and were ineligible; 26 chose to join the study. The cumulative life-table response rate during the 12-month observation period was 70.8%; adequate immune response was linked to survival, 73% in survivors completing the study and 9% in nonsurvivors. Adverse effects were minor. We conclude that hepatitis B vaccine is safe and usually effective in inducing immunity in oncology patients younger than 60 years of age who are receiving chemotherapy.
A characteristic pattern of leukemic cell differentiation without cytoreduction during remission induction in acute promyelocytic leukemia.
Authors: Kantarjian H M , Keating M J , McCredie K B , Beran M , Walters R , Dalton W T , Hittleman W , Freireich E J
Published: February 2017

While differentiation of leukemic cells in vitro is well established, the role of differentiation in vivo is not defined and is generally attributed to differentiation inducers. In five patients with acute promyelocytic leukemia (APL) an unusual pattern of a slow and progressive decrease of immature blasts with a concomitant increase in mature cellular elements was observed following intensive combination chemotherapy. All patients eventually achieved complete remission, four of them without an intermediate phase of marrow hypoplasia. This morphologic pattern of response suggests that leukemic cellular differentiation rather than cytotoxicity was one mechanism involved in remission induction. Cytogenetic studies of remission revealed disappearance of the cytogenetic marker, the balanced translocation between the long arms of chromosomes 15 and 17. This remission induction process appears to be due to the cellular biologic characteristic rather than the therapy used as it occurs in a substantial proportion of patients with APL. It should be considered for optimal diagnostic and therapeutic decisions.