bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in central nervous system leukemia with a pharmacokinetically derived intrathecal methotrexate dosage regimen.
Authors: Bleyer W A , Coccia P F , Sather H N , Level C , Lukens J , Niebrugge D J , Siegel S , Littman P S , Leikin S L , Miller D R
Published: February 2017

During the period 1976-1981, 3241 children were enrolled on three major studies of acute lymphoblastic leukemia by participating institutions of the Children's Cancer Study Group. Each study included a different method of central nervous system (CNS) prophylaxis: (1) standard therapy with cranial irradiation, 2400 rads, and intrathecal methotrexate at 12 mg/m2 six times during consolidation (CCG-141); (2) a modification of CCG-141 in which the intrathecal methotrexate was initiated during induction (CCG-141A); and (3) a reduced cranial irradiation dose of 1800 rads with intrathecal methotrexate given at the same frequency as a CCG-141A, with or without maintenance intrathecal methotrexate, but with a dosage regimen derived from CNS volume considerations rather than based on body surface area (CCG-160 series). Strategy 3, a change in the intrathecal methotrexate dosage, has resulted in the lowest incidence of CNS leukemia to date (p less than 0.007). The cumulative 3-yr CNS relapse rate has decreased from 8%-10% to 2%-5% in average-risk patients (p less than 0.02; life table estimate) and from 23%-27% to 6% in high-risk patients (p less than 0.0002; life table estimate), despite a reduction in the cranial irradiation dose from 2400 to 1800 rads. Maintenance intrathecal chemotherapy has had a marginal effect among patients randomized to receive this additional therapy (p = 0.06). The overall outcome has been an increase in the continuous complete remission rate (p = 0.04) but not in the estimated 3-yr continuous hematologic remission or survival rates.
Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer.
Authors: Logothetis C J , Samuels M L , von Eschenbach A C , Trindade A , Ogden S , Grant C , Johnson D E
Published: February 2017

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.
Sequential changes in platelet function and coagulation in leukemic children treated with L-asparaginase, prednisone, and vincristine.
Authors: Pui C H , Jackson C W , Chesney C , Lyles S A , Bowman W P , Abromowitch M , Simone J V
Published: February 2017

Coagulation and platelet function in 13 children with acute lymphoblastic leukemia were studied sequentially during a remission induction with L-asparaginase, prednisone, and vincristine. In the first weeks of therapy, which included four doses of L-asparaginase coagulation was characterized by significant decreases in plasma concentrations of plasminogen, antithrombin III alpha 2-macroglobulin, and fibrinogen. All measures gradually returned to normal after complication of L-asparaginase therapy. In the latter part of induction treatment, clotting times, especially partial Thromboplastin time, decreased significantly, while levels of factors V and VIII increased with recovery of platelet counts. At this time, 6 patients had an increased in vitro platelet aggregation response to adenosine diphosphate, and their partial thromboplastin times were significantly shorter than those of patients without increased aggregation. Concurrent abnormalities in coagulation and platelet function may account for the thrombotic complications that develop in some children receiving induction therapy with these agents.
Peritoneal mesothelioma: natural history and response to chemotherapy.
Authors: Antman K H , Pomfret E A , Aisner J , MacIntyre J , Osteen R T , Greenberger J S
Published: February 2017

Twenty-three patients with malignant peritoneal mesothelioma seen at the Dana Farber Cancer Institute and the University of Maryland Cancer Center from 1968 to 1982 were studied to assess the natural history of the disease and the efficacy of current treatment. Asbestos exposure was reported by 57%. Of 18 patients receiving a doxorubicin-containing regimen, 14 had measurable or evaluable disease. One complete response, four partial responses and one regression (in a patient with evaluable but not measurable disease) were observed, ranging in duration from 6 to 36 months. A single patient remains disease free for more than 36 months after subsequent radiotherapy. Significant clotting abnormalities (including disseminated intravascular coagulation, massive thrombosis, fatal pulmonary emboli, Coombs-positive hemolytic anemia, and phlebitis) occurred in 22% of the patients. Trends toward decreased survival were observed for smokers, patients presenting with ascites, and those with stage II-IV disease.
Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study.
Authors: Salmon S E , Haut A , Bonnet J D , Amare M , Weick J K , Durie B G , Dixon D O
Published: February 2017

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.
Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy.
Authors: Goodman G E , Miller T P , Manning M M , Davis S L , McMahon L J
Published: February 2017

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.
Involvement of the genitourinary system in multiple primary malignant neoplasms: a review.
Authors: Ray P , Sharifi R , Ortolano V , Guinan P
Published: February 2017

A case is presented of a patient with separate primaries of the cervix, breast, bladder, and kidney. In a review of 352,073 cancer patients in the literature, the genitourinary system appears to be at a greater risk of this phenomenon. The entity of multiple primary malignant neoplasms is reviewed with an analysis of the involvement of the genitourinary system.
Monoclonal antibodies in cancer therapy.
Authors: Oldham R K
Published: February 2017

The need for improved specificity in cancer therapy is apparent. With the advent of monoclonal antibodies, the possibility of specifically targeted therapy is being considered. Early trials of monoclonal antibody in experimental animals and humans have indicated its ability to traffic to specific tumor sites and to localize on or around the tumor cells displaying antigens to which the antibody is directed. This evidence of specific targeting, along with preliminary evidence of therapeutic efficacy for monoclonal antibodies and immunoconjugates with drugs, toxins, and isotopes is encouraging. The current status of clinical trials with monoclonal antibodies is reviewed and an example of the experimental approach for the development of immunoconjugates in animal models is presented.
Gene amplification in a leukemic patient treated with methotrexate.
Authors: Horns R C , Dower W J , Schimke R T
Published: February 2017

Resistance to methotrexate (MTX) has been shown in mouse, hamster, and human cell lines grown in sequentially increased MTX concentrations to be due to increased dihydrofolate reductase (DHFR) synthesis and a proportional increase in DHFR gene copy number. Leukemia cells of a patient were studied to assess change in DHFR gene copy number after MTX treatment. The patient presented with chronic myeloid leukemia which rapidly evolved into blast crisis; 90% of peripheral white cells were lymphoblasts. Treatment included intrathecal and intravenous MTX; the lymphoblasts were reduced to undetectable levels. Three months later a second blast crisis occurred; 90% of peripheral white cells were lymphoblasts. Cells from each blast crisis were obtained by leukapheresis and stored for study. Quantification of DHFR gene copy number in DNA from lymphoblasts before and after MTX treatment was done: a radiolabeled cloned cDNA constituting the mouse DHFR coding sequence was used to probe high molecular weight pretreatment and posttreatment DNA bound to nitrocellulose filters. Posttreatment DNA contained two- to three-fold more DHFR gene sequences than pretreatment DNA. Quantitative Southern blotting of EcoRI-digested pretreatment and posttreatment DNA confirmed amplification of the DHFR gene. Karyotype analysis showed no double minute chromosomes or homogeneously staining regions. This is the first study demonstrating DHFR gene amplification in leukemia cells sampled in vivo from a patient treated with MTX.
Time course and prognosis of local recurrence following primary radiation therapy for early breast cancer.
Authors: Harris J R , Recht A , Amalric R , Calle R , Clark R M , Reid J G , Spitalier J M , Vilcoq J R , Hellman S
Published: February 2017

The frequency, time course, and prognosis of local recurrence following primary radiation therapy in 152 patients with early breast cancer treated before 1967 were examined. Local recurrence occurred at a constant rate over the first 14 years after treatment. The crude 15-year local recurrence rate was 22%. Of the 30 patients who developed an isolated local recurrence and underwent definitive secondary surgery, the 10-year freedom from distant relapse rate was 50%. These results indicate that breast cancer patients treated by primary radiation therapy require long-term follow-up to detect curable local recurrences.
Elevated myelin basic protein levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia.
Authors: Mahoney D H , Fernbach D J , Glaze D G , Cohen S R
Published: February 2017

Cerebrospinal fluid was examined from 70 children with acute lymphoblastic leukemia for evidence of active myelin breakdown based on the release of myelin basic protein (MBP). Fifty-three asymptomatic children were followed from diagnosis with serial MBP determinations. Eight (15.1%) of 53 children had abnormal elevations of MBP, six of eight before receiving presymptomatic central nervous system therapy. Long-term observations are in progress. For comparison, six children with clinical and radiologic findings of leukoencephalopathy had abnormal MBP determinations, whereas no abnormalities were detected in 11 children with meningeal leukemia.
Analysis of serum free light chains by crossed immunoelectrophoresis: comparison with urinary light chains in light chain disease.
Authors: McLeod B C , Viernes A , Kyle R A , Sassetti R J
Published: February 2017

We investigated the relationship between serum free light chain levels measured by crossed immunoelectrophoresis in ten patients with light chain disease and traditional 24-hour urinary light chains in the same patients. The crossed immunoelectrophoresis test requires only a venipuncture for specimen acquisition, can be completed within 24 hours, and has a reproducibility (+/- 14%) comparable with that of other immunoprecipitin techniques. Twenty-eight serum-urine pairs, representing 18 discrete intervals, were analyzed. There was a close relationship between changes in serum and urine light chain levels, with a correlation coefficient of .77 or .93, depending on the method of calculation. This suggests that serum light chain levels measured by crossed immunoelectrophoresis would be equivalent to urinary light chain levels as indicators of tumor burden. Monitoring serum levels would have the advantage of greatly simplified specimen acquisition. In patients with renal failure, serum light chain levels should be a superior indicator of light chain synthesis.
Nutritional parameters affecting erythrocyte polyamine levels in cancer patients.
Authors: Ota D M , Nishioka K , Foulkes M , Grossie V B
Published: February 2017

Changes in erythrocyte polyamine levels during intravenous hyperalimentation in cancer and noncancer patients were determined, and the influence of host nutritional status on polyamine metabolism was analyzed. RBC putrescine (P less than .001), spermidine (P less than .01), and spermine (P less than .005) levels, and the putrescine-spermidine ratio (P less than .001) increased in the cancer group while no significant increases were noted in the noncancer group. The degree of malnutrition, based on body weight loss and plasma albumin, transferrin, prealbumin, and retinol-binding protein levels, was significantly greater in the cancer group than in the noncancer group, giving rise to the possibility that repletion of nutritional deficits in host tissues could have contributed to the rise in RBC polyamines. When cancer patients of similar nutritional status were matched with the noncancer group, increases in RBC putrescine level and putrescine-spermidine ratio were noted in the selected cancer patients. These results suggest that correction of nutritional deficits did not contribute significantly to the RBC polyamine pool and that increases in RBC polyamines during intravenous hyperalimentation were related to the presence of tumor.
The effect of specific and nonspecific immunotherapy on natural killer cell activity in patients with non-small-cell lung cancer.
Authors: Maroun J A , Pross H F , Stewart T H , White M J , Hyslop D B
Published: February 2017

Fourteen patients with stages I and II non-small-cell lung carcinoma receiving adjuvant immunotherapy after surgery were studied serially for natural killer (NK) cell cytotoxicity assays. Seven patients received active nonspecific immunotherapy with Freund's complete adjuvant alone and seven patients received active specific immunotherapy with tumor-associated antigen plus Freund's complete adjuvant. Both groups were analyzed as a single group in view of the lack of any difference in the results. The results indicated that NK-cell cytotoxicity v K562 was lower in untreated patients than in normal controls, but the difference was not significant. There was no evidence of specific cytotoxicity v the lung cell line A549 in untreated patients when compared with normal controls. Compared with pretreatment values, elevated cytotoxicity v both K562 and A549 was observed at every post-treatment time point tested, and this was statistically significant at several time points by a paired t test. No specific effect was noted after immunization with lung antigen on cytotoxicity against the lung cell line A549. Other correlations studied did not show any relationship between delayed hypersensitivity skin testing or serum carcinoembryonic antigen levels and NK-cell cytotoxicity. It is concluded that NK-cell reactivity was increased nonspecifically by active specific and nonspecific immunotherapy. This increase seems to peak at the 12-month period and was significant when compared with pretreatment levels.
Malignant melanoma in childhood: clinical course and response to chemotherapy.
Authors: Hayes F A , Green A A
Published: February 2017

Malignant melanoma is uncommon in patients less than 20 years of age, and little is known about the response to chemotherapy in this age group. We report here a series of 18 children, of whom ten with metastatic disease were treated with cyclophosphamide, vincristine, and dactinomycin. Only two of nine evaluable patients failed to show an objective response to therapy. Five of ten patients treated are alive and free of tumor 12 to 80 months from the start of chemotherapy. Three have been in remission for more than five years. Results suggest that melanoma in this age group may be more responsive to chemotherapy than melanoma in adult patients and that a trial of this therapy in a larger number of children with evaluable disease is warranted.
5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract.
Authors: Harvey J H , Smith F P , Schein P S
Published: February 2017

A phase II trial of the regimen 5-fluorouracil, doxorubicin, and mitomycin C (FAM) was conducted in 17 patients with advanced or recurrent biliary tract cancer. Among 14 patients with measurable disease, 31% achieved a partial response. An additional seven patients evidenced stabilization of disease for periods of three to 18+ months. One patient with advanced but unmeasurable tumor has survived 72 months after 12 cycles of treatment. There was no serious life-threatening toxicity, and with appropriate dosage adjustment, the drug was administered to patients with mild hepatic insufficiency. We recommend the initiation of a larger controlled trial and a potential application with radiotherapy for patients with less advanced disease.
Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma.
Authors: Moertel C G , Childs D S , O'Fallon J R , Holbrook M A , Schutt A J , Reitemeier R J
Published: February 2017

Sixty-two patients with resectable but poor-prognosis gastric carcinoma were randomized to either no surgical adjuvant therapy or treatment with 5-fluorouracil (15 mg/kg by rapid intravenous injection X 3) plus radiation (3,750 rad in 24 fractions) initiated 3 1/2 to six weeks postoperatively. Informed consent was obtained after randomization and only from the 39 randomized to treatment. Ten patients refused their treatment assignment. The five-year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P less than .05). Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups (P = .024) and favored treatment assignment. When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing, five-year survival rates were: treated, 20%; treatment refusal, 30%; controls, 4%; the three survival distributions were not significantly different. Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54% of those who received no treatment. This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research. This study also illustrates the potential problems that may be encountered in interpreting results when patients are randomized to a study before consent is obtained.
Alternating combination chemotherapy for stages III and IV ovarian carcinoma.
Authors: Young J A , Johnson A , Kroener J , Koziol J A , Saltzstein S , Yon J L , Campbell T N , Lucas W , Green M R
Published: February 2017

Thirty-nine previously untreated patients with stages III and IV ovarian carcinoma were treated with debulking surgery, followed by alternating combination chemotherapy with cisplatin, Adriamycin (Adria Laboratories, Columbus, Ohio), and cyclophosphamide (PAC); and hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (HexaCAF). Of 19 patients with measureable disease at the onset of therapy, ten (53%) had at least a partial response to chemotherapy. Seven (18% of total) patients were found to be pathologically free of disease at secondlook surgery, but four patients relapsed 19 to 31 months after initiating therapy. The median progression-free survival period of all 39 patients entered into the study is 12 months, and the median crude survival is 21 months. The PAC/HexaCAF alternating combination chemotherapy regimen may be administered with moderate toxicity, but the treatment results are not superior to those reported for PAC or HexaCAF alone in advanced ovarian carcinoma.
Randomized study of systemic chemotherapy following complete excision of nonosseous sarcomas.
Authors: Edmonson J H , Fleming T R , Ivins J C , Burgert E O , Soule E H , O'Connell M J , Sim F H , Ahmann D L
Published: February 2017

Between June 1975 and April 1981, 61 of the 177 eligible patients whose nonosseous sarcomas of extremity or trunk origin had been completely excised primarily or after local recurrences agreed to participate in a randomized study of adjuvant chemotherapy. Dermatofibrosarcoma, lymphomas, myeloma, Kaposi's sarcoma, and embryonal rhabdomyosarcoma were excluded as were patients with significant second primary cancers and those who received either preoperative or postoperative radiation therapy. After stratification by anatomic status of disease, site of origin, and histologic grade, a random one half of the 61 participants began alternating courses of vincristine/cyclophosphamide/dactinomycin, and vincristine/doxorubicin/dacarbazine at six-week intervals for one year. The control group was evaluated at six-week intervals without adjuvant chemotherapy, but these patients were offered this chemotherapy later if they had progressive disease excised. Although 30% of the 61 patients experienced local recurrence of disease within the first five years after randomization, and only 54% were continuously disease free for five or more years, 82% were surviving at five years (Kaplan-Meier calculations) with a median follow-up of 64.3 months. Partial suppression of distant metastasis by adjuvant chemotherapy was apparent in the overall study, in the extremity tumor category, and in the subgroup of patients who had received limb-sparing surgery; however, no survival advantage for chemotherapy-treated patients was demonstrated. The 30 adjuvant chemotherapy-treated patients received a total of three thoracotomies as compared with 17 salvage thoracotomies for the 31 control patients; however, salvage surgery for local recurrences has been similar in the two groups. Recent improvement in the survival of patients with soft-tissue sarcomas is not necessarily a result of adjuvant chemotherapy or radiation therapy.
Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain control.
Authors: Coombs D W , Maurer L H , Saunders R L , Gaylor M
Published: February 2017

Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.
A comparison of cardiac biopsy grades and ejection fraction estimations in patients receiving Adriamycin.
Authors: Ewer M S , Ali M K , Mackay B , Wallace S , Valdivieso M , Legha S S , Benjamin R S , Haynie T P
Published: February 2017

One hundred fifty-eight patients receiving Adriamycin underwent 226 transjugular biopsy procedures. The specimens were evaluated by electron microscopy for evidence of drug-related cardiotoxicity. Ejection fraction determinations using echocardiographic or nuclear techniques at rest were available for 69% and 81% of the patients, respectively. Analysis of the data revealed a correlation between cumulative Adriamycin dose and biopsy grade (p less than 0.02). No similar relationship existed between cumulative Adriamycin dose and ejection fractions obtained at rest or between biopsy grades and ejection fractions. In patients who underwent serial endomyocardial biopsies and serial ejection fraction determinations, the correlation between changes in biopsy grade and ejection fraction was poor. A change in resting ejection fraction detected by either method did not reliably predict a change in biopsy grade. The poor correlation between ejection fractions and biopsy grades could be due in part to the sensitivity and specificity of the Adriamycin-related structural changes in contrast to the wider range of disease processes that can affect myocardial function, and to the fact that structural changes often precede the ejection fraction abnormalities. The greater sensitivity and specificity of the biopsy grade should prove useful in reducing the risks associated with evaluating new anthracyclines and potential myocardial protectors of Adriamycin toxicity.
Criteria for monitoring carcinoembryonic antigen: variability of sequential assays at elevated levels.
Authors: Lokich J J , Ellenberg S , Gerson B
Published: February 2017

Fifty-five patients with advanced cancer and elevated plasma carcinoembryonic antigen (CEA) levels greater than 20 ng/mL (Roche assay) were monitored by clinical parameters for disease activity and a daily plasma specimen was obtained and stored frozen. In 45 patients with evaluable metastatic lesions, 35 were stable; five had progressive disease; and five had regressive disease. Plasma CEA in patients with stable disease showed an overall coefficient of variation of 13%. The CV did not differ according to various quantitative CEA levels from less than 100 ng/mL to greater than 1,000 ng/mL. The coefficient of variation in responding and progressive disease patients ranged from 13% to 63%. An analysis of CEA variability relative to the baseline CEA level was possible using the formula square root 2 times the variability about the mean; this yields a value of +/- 36% representing the range within which approximately 95% of sequential CEA levels would lie in the absence of a clinical change in disease. In 225 CEA determinations in stable disease patients, 6% demonstrated an increase beyond this level (36%) and none demonstrated a decrease of 36% or more from the baseline level. This study establishes guidelines for the boundaries of change in plasma CEA that may be applied as a criterion (in conjunction with standard objective disease parameters) for determination of tumor response to therapy.
Small cell bronchogenic carcinoma: factors associated with pneumonia during chemotherapy.
Authors: Dixon C L , Valdivieso M , Umsawasdi T , Dubois G , Patton D , Chen T , Ali M K , Bodey G P
Published: February 2017

Sixty-five patients with small cell bronchogenic carcinoma were treated with intensive induction chemotherapy and supportive treatment. The clinical course of 43 patients who had pretreatment spirometry and arterial blood gases was studied. Thirteen patients developed pneumonia. Moderate hypoxemia, advanced age, and a low forced expiratory flow 25%-75% were associated with the development of pneumonia. Endobronchial obstruction and neutropenia, other factors associated with infection in cancer patients, appeared to be less important in this patient population.
Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration.
Authors: Postmus P E , Holthuis J J , Haaxma-Reiche H , Mulder N H , Vencken L M , van Oort W J , Sleijfer D T , Sluiter H J
Published: February 2017

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.
Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.
Authors: Rozencweig M , ten Bokkel Huinink W , Cavalli F , Bruntsch U , Dombernowsky P , Høst H , Bramwell V , Renard G , Van Glabbeke M , Decoster G
Published: February 2017

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.
The natural history of gastric cancer and prognostic factors influencing survival.
Authors: Bedikian A Y , Chen T T , Khankhanian N , Heilbrun L K , McBride C M , McMurtrey M J , Bodey G P
Published: February 2017

This study of 783 patients with histologically confirmed gastric carcinoma has confirmed the importance of several previously recognized patient- and tumor-related characteristics related to prognosis and identified some new ones. Of the tumor-related factors, the ones that showed the strongest relationship to survival following curative gastric resection were tumor stage, histologic type, breach of lymph-node capsule, sinus histiocytosis, and gross appearance. Of the tumor- and patient-related factors, the ones that showed the strongest relationship to survival from time of diagnosis of surgically noncurable disease were status of primary, liver metastasis, serum bilirubin level, ascites, extent of tumor burden, and weight loss. The effect of treatment with 5-fluorouracil (5-FU) on survival duration was at best only minimal. Only those patients who received two or more cycles of 5-FU therapy had survival advantage over the remaining patients. The use of regression analysis has made it possible to make predictions of the prognosis of the patients. These predictions could be used in future studies to determine comparability of prognosis of various groups included in different studies and different arms of a randomized study.
Interferons in the treatment of human cancer.
Authors: Kirkwood J M , Ernstoff M S
Published: February 2017

The interferons are the best known of biologic antineoplastic agents. Progress with the clinical application of interferons to cancer has been slow and complicated by the need for attention to a new spectrum of therapeutic and toxic effects manifest by the interferons. This summary of current phase I and II trial results with the interferons establishes their clinical potential. The maximally tolerated dosages of the most common species of interferon alpha produced in eukaryotic cells as well as by recombinant DNA technology in bacteria are now described in a variety of different disease states. "Naturally" produced eukaryotic as well as bacterially synthesized interferons have a similar, wide range of biologic effects in vitro and in vivo. Antiviral, antiproliferative, immunologic, and enzymologic functions of the interferons relevant to antineoplastic functions are under study. Knowledge of these mechanisms should improve the clinical results obtained in human cancer. Species and subspecies differences in the activity of interferons may lead to selective use of the pure interferon subspecies, alone or in combination. The use of the interferons and other antineoplastic biologics, such as antibody or chemotherapy, are subsequent goals that are now on the horizon.
Treatment of meningeal relapse in childhood acute lymphoblastic leukemia. I. Results of craniospinal irradiation.
Authors: Kun L E , Camitta B M , Mulhern R K , Lauer S J , Kline R W , Casper J T , Kamen B A , Kaplan B M , Barber S W
Published: February 2017

Fourteen children were treated for isolated meningeal relapse occurring seven to 44 months (median, 14 months) after prophylactic cranial irradiation (2,400 rad/12 fractions) and intrathecal methotrexate (IT MTX, 12 mg/m2 for four doses during cranial irradiation). Eight had "high-risk" acute lymphocytic leukemia with age less than 2 years, white blood cell counts greater than 20,000, or T cell markers. Treatment for central nervous system leukemia included IT MTX (12 mg/m2 twice weekly until clearance of spinal fluid cytology) followed by craniospinal irradiation (CSI, 3,000 rad/20 fractions to the cranium and 1,800 rad/12 fractions to the spine). No maintenance IT MTX was given. Systemic chemotherapy was continued or reinstituted for a minimum of one year after CSI. No instance of second meningeal relapse has occurred. Five patients remain in secondary complete remission 66+, 54+, 36+, 26+, and 24+ months after meningeal relapse. Disease-free survival was limited by marrow relapse in eight patients (2-20 months after CSI) and testicular relapse in one. No acute toxicities were noted with CSI. Myelosuppression occurred in seven patients. Infections within two months of CSI were noted in five. No neurologic sequelae are apparent. Serial neuropsychometric studies in 10 patients revealed a significant decline in mean values on Global IQ scales. Long-term survival with acceptable toxicity is possible following aggressive, prompt treatment of meningeal relapse occurring after prophylactic cranial irradiation. Hematologic relapse remains the major obstacle to long-term disease-free survival.
Phase I and II trial of five-day infused 5-fluorouracil and radiation in advanced cancer of the head and neck.
Authors: Byfield J E , Sharp T R , Frankel S S , Tang S G , Callipari F B
Published: February 2017

Eighteen patients with advanced epithelial cancers of the head and neck region were studied for their tolerance and response to combined cycles of 120-hour infused 5-fluorouracil (5-FU) and external-beam radiation therapy. 5-FU infusions were given under conditions where radiosensitization would be expected at the higher infusion doses. Coincident radiation treatments were given as four sequential daily fractions of 250 rad each administered during days 1 through 4 of each five-day infusion cycle. The patients were rested for at least nine days after each cycle or longer until toxicity was resolved. The regimen was then repeated in each patient for a total of five treatment cycles. Thereafter therapy was consolidated, usually by boost radiation without drug. In sequential patient subsets the infusion load was progressively escalated in a phase I format. The complete response rate for stage IV patients was 75% with survival benefit compared to prior results. 5-FU dose-dependent combined modality loco-regional toxicity was demonstrated without significant enhancement of systemic toxicity of any form; 5-FU dose-dependent enhanced responsiveness and survival benefit is also suggested. Further scheduling and response studies of 5-FU under radiosensitizing conditions appear warranted.
Etoposide (VP-16-213) in malignant brain tumors: a phase II study.
Authors: Tirelli U , D'Incalci M , Canetta R , Tumolo S , Franchin G , Veronesi A , Galligioni E , Trovò M G , Rossi C , Grigoletto E
Published: February 2017

Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide (VP-16-213) (50-100 mg/m2 for five days every three weeks). Response, defined as improvement in both clinical examination and computed tomography scan in absence of glucocorticoids dosage increase, was observed in three (17%) of 18 evaluable patients, lasting greater than 21, seven, and two months, respectively. Six additional patients had stable disease for greater than 10, seven, four, four, three, and two months: all of them had improvement of clinical symptoms but no variation in their scans. Overall median survival from the start of VP-16-213 was 4.5 months (range, 1-23 + months), whereas patients with response or stable disease had a median survival of eight months. Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid chromatographic method for drug assay. The concentration of VP-16-213 in cerebrospinal fluid was less than 1% that found in plasma, even in the two patients with response. The activity of etoposide in patients with malignant, lomustine-vincristine-resistant brain tumors suggests an interesting potential use for this drug.
Hemolytic transfusion reactions in oncology patients: experience in a large cancer center.
Authors: Lichtiger B , Perry-Thornton E
Published: February 2017

At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, the incidence of hemolytic transfusion reactions over an eight-year period (1974-1981) was analyzed. Only four hemolytic transfusion reactions were reported out of 142,957 transfusions of blood (a frequency of one reaction in 35,739.25 transfusions). This could be due to the following factors: (1) Impairment of immune status related to the malignant process or temporary immunosuppression caused by intensive chemotherapy could enable patients to tolerate incompatible transfusions. (2) The reactions are overlooked or masked by the severity of disease in cancer patients in spite of an elaborate education for nurses, residents/fellows, and staff physicians about the dangers of hemolytic reactions. The figures herein reported are lower than those reported from non-oncology hospital settings.
Endomyocardial biopsy to monitor anthracycline therapy in children.
Authors: Pegelow C H , Popper R W , de Wit S A , King O Y , Wilbur J R
Published: February 2017

Evaluation of the ultrastructure of material obtained by endomyocardial biopsy has been proposed as a means to evaluate patients for impending anthracycline cardiotoxicity. Eighteen biopsies obtained from 13 patients (age, 3-18 years) are reported. Twelve biopsy procedures were done to evaluate the cardiac status on reaching a cumulative dose of 400 mg/m2 and three patients had six subsequent biopsies after having received significantly more drug or receiving radiation therapy to the lungs or mediastinum. Scores were assigned to the tissue obtained and used to guide the decision to continue or stop anthracycline therapy. Three patients with abnormal cardiac studies at low cumulative doses, five of whom had received greater than 400 mg/m2 and three of whom had received considerably higher doses and thoracic irradiation were given more drug without incident. Two specimens were interpreted to indicate avoidance of further anthracycline and two patients were cautiously given more despite evidence of mild myocardial damage. These results indicate that endomyocardial biopsies can be performed on a pediatric population with a reasonable complication rate. Further studies should be undertaken to evaluate its usefulness as a means to predict and avoid anthracycline cardiomyopathy.
Pharmacologic rationale for regional drug delivery.
Authors: Collins J M
Published: February 2017

Regional drug delivery is an approach designed to improve the selectivity of chemotherapy. When compared with systemic drug administration, regional delivery can potentially increase drug concentrations at tumor sites and/or lower systemic drug exposure. Pharmacokinetic analysis can evaluate or even predict the relative advantage of regional drug delivery. Based on a quantitative analysis of regional drug delivery, some drugs and sites of delivery are more favorable than others. The formulas for the therapeutic advantage of intraarterial, intrathecal, and intraperitoneal delivery have a similar structure. The ratio of total body clearance of a drug to its regional exchange rate is the principal determinant of therapeutic advantage. Thus, the most favorable circumstances for regional delivery are the use of drugs with high total body clearances and/or sites of delivery with low exchange rates. Pharmacodynamic factors must also be considered for the overall assessment of regional delivery.
Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy.
Authors: da Cunha M F , Meistrich M L , Fuller L M , Cundiff J H , Hagemeister F B , Velasquez W S , McLaughlin P , Riggs S A , Cabanillas F F , Salvador P G
Published: February 2017

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.
Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma.
Authors: Kemeny N , Daly J , Oderman P , Shike M , Chun H , Petroni G , Geller N
Published: February 2017

5-Fluorodeoxyuridine (FUDR) was infused continuously into the hepatic artery for 14 days a month at an initial dose of 0.3 mg/kg per day in 45 patients with liver metastases from colorectal carcinoma. In 41 adequately treated patients, partial responses (greater than 50% tumor regression) were observed in 12 (52%) of 23 previously untreated patients, and three (17%) of 18 previously treated patients. Severe gastrointestinal toxicity was endoscopically documented in 19 (46%) patients; 12 (29%) had discrete ulcers, and seven had diffuse gastritis or duodenitis. Significant hepatic-enzyme abnormality was seen in 29 patients (71%) and an elevated serum bilirubin in nine (22%). A significant factor influencing survival was the extent of tumor involvement in the liver; patients with less than 20% involvement have not yet reached a median survival at 13 months versus six months for patients with greater than 60% involvement (p less than 0.001). Studies comparing regional to systemic chemotherapy and stratifying patients according to the extent of hepatic tumor burden are needed to assess the true impact of hepatic infusion on response and survival.