bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical trial of sequential N-phosphonacetyl-L-aspartate, thymidine, and 5-fluorouracil in advanced colorectal carcinoma.
Authors: O'Connell M J , Moertel C G , Rubin J , Hahn R G , Kvols L K , Schutt A J
Published: February 2017

Preclinical studies have demonstrated enhanced cytotoxic effects of 5-fluorouracil (5-FU) when given in conjunction with N-phosphonacetyl-L-aspartate (PALA) or thymidine in several murine systems. Early clinical studies have demonstrated significant delayed depletion of pyrimidine nucleotides in tumor biopsy specimens following systemic PALA administration and prolonged serum levels of 5-FU after thymidine administration. Each of these biochemical effects would be anticipated to augment the cytotoxic activity of 5-FU. A phase II trial of a timed sequential administration schedule of PALA, thymidine, and 5-FU was conducted in 37 patients with advanced measurable colorectal cancer. Ten of 37 patients (27%) experienced objective tumor responses with a median response duration of 22 weeks, and 18 patients (49%) had stable disease for a median duration of 20 weeks. Six of 13 patients (46%) with anaplastic histology and/or rapidly progressive tumors experienced high-quality tumor responses. Leukopenia and neurologic side effects were the primary toxicities, including one death caused by sepsis. This regimen has demonstrated striking alteration in the 5-FU dose-effect relationship and definite antitumor activity in patients with advanced colorectal cancer. Further trials in patients with anaplastic carcinomas of the colon or other anatomic sites should be considered.
Tumor-associated peripheral eosinophilia: two unusual cases.
Authors: Reddy S S , Hyland R H , Alison R E , Sturgeon J F , Hutcheon M A
Published: February 2017

Peripheral eosinophilia is a rare but recognized accompaniment of malignant disease. Two unusual cases, one with a histiocytic lymphoma and the other with cervical carcinoma, are described. In the first patient, pulmonary infiltrates developed at the height of the eosinophilia and in the second, the peripheral eosinophilia heralded the onset of disseminated disease. Tumor-associated peripheral eosinophilia is reviewed, and it is concluded that peripheral eosinophilia associated with a malignant setting is a marker of extensive disease and is thus associated with a poor prognosis.
Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor.
Authors: Engstrom P F , Lavin P T , Moertel C G , Folsch E , Douglass H O
Published: February 2017

EST 5275 is a phase II and III study of fluorouracil plus streptozocin (5-FU plus STZ) or doxorubicin in patients with measurable progressive carcinoid tumor. Among one hundred seventy-two cases with no prior chemotherapy and no heart disease, the response rate was 22% for 5-FU plus STZ and 21% for doxorubicin, while the median response duration and median survival were 31 weeks and 64 weeks for the combination and 26 weeks and 48 weeks for doxorubicin. Thirty-three patients who failed 5-FU plus STZ crossed over to doxorubicin and achieved an 18% response. Of the thirty-five patients who failed on doxorubicin, 29% responded to 5-FU plus STZ. Hematologic toxicity was similar for both treatments; however, the 5-FU plus STZ patients experienced more vomiting but acceptable renal toxicity. Both chemotherapy regimens have antitumor activity in carcinoid tumors.
Pulmonary uptake of technetium 99m macroaggregated albumin: a predictor of gastrointestinal toxicity during hepatic artery perfusion.
Authors: Kaplan W D , Come S E , Takvorian R W , Laffin S M , Gelman R S , Weiss G R , Garnick M B
Published: February 2017

Hepatic artery infusion of 5-fluoro-2-deoxyuridine (5-FUdR) provides high hepatic drug levels but little systemic toxicity, since, by this route of administration, the drug is detoxified by the hepatocytes. Slow infusion of technetium 99m- (99mTc) labeled macroaggregated albumin (MAA) through the hepatic artery is an aid in catheter placement, in predicting response of liver metastases to therapy, and in identifying extra-hepatic flow in the gastroduodenal or splenic arteries as an indicator of systemic toxicity. Marked pulmonary uptake of this tracer after slow radionuclide hepatic angiography was noted in four patients who showed major gastrointestinal (GI) toxicity. A retrospective examination of pulmonary accumulation of 99mTcMAA as a predictor of GI toxicity is the subject of this paper. Two groups of patients were evaluated. The first group consisted of 14 consecutive patients in whom continuous infusion of drug was administered by an external pump by way of a percutaneous catheter. Patients received baseline and follow-up (seven to 27 days) slow-infusion tracer studies (2 to 4 mCi 99mTcMAA at 10 to 21 mL/h). The second group included 14 consecutive patients who were receiving intraarterial chemotherapy by a totally implantable pump system. All received baseline slow-infusion studies (2 to 4 mCi 99mTcMAA at approximately 0.5 to 1.0 mL/min). The percentage of the injected dose in the lung was determined. Patients with greater than 20% of tracer in the lung after radionuclide hepatic angiography had significantly greater severe GI toxicity than patients with baseline values of less than 20%. Our findings support the existence of hepatic arteriovenous (A-V) communications in some patients and suggest that they are present pretherapy. Presence of these A-V communications, which can result in a vascular bypass of normal hepatic parenchyma and the subsequent decrease in hepatic detoxification of chemotherapeutic agents, is the likely cause of GI toxicity. Pulmonary uptake of tracer injected in the hepatic artery may be useful in quantifying the degree of shunting and facilitate the monitoring of potential systemic toxicity.
Totally implantable system for peritoneal access.
Authors: Pfeifle C E , Howell S B , Markman M , Lucas W E
Published: February 2017

A totally implantable system for providing access to the peritoneal cavity was evaluated. Fifty-six Port-A-Cath (Pharmacia Nu Tech, Piscataway, NJ) peritoneal access systems were implanted in 54 cancer patients receiving intraperitoneal chemotherapy. The catheters are accessed by transcutaneous placement of a Huber point needle through a silicone septum at the top of the portal. A total of 32 patient years of experience are reported. The Port-A-Caths have been in place for a median of 22 weeks (range, one to 85). A total of 401 entries have been made for paracentesis, chemotherapy administration, antibiotic administration, peritoneal lavage for cytology, and catheter flushing. There have been six episodes of peritonitis (five Staphylococcus epidermidis, one S aureus) in three patients. There have been no mechanical failures of the Port-A-Caths. Loss of bidirectional flow through the catheter due to fibrin deposition about the catheter has been the major cause of catheter failure. Patient acceptance of the Port-A-Cath has been excellent.
Combination intraperitoneal chemotherapy with cisplatin, cytarabine, and doxorubicin for refractory ovarian carcinoma and other malignancies principally confined to the peritoneal cavity.
Authors: Markman M , Howell S B , Lucas W E , Pfeifle C E , Green M R
Published: February 2017

Thirty-one patients with refractory ovarian cancer and other malignancies principally confined to the abdominal cavity were treated with an intraperitoneal combination-chemotherapy regimen consisting of cisplatin (100 to 200 mg/m2), cytosine arabinoside (10(-4) to 10(-3) mol/L) and doxorubicin (2 to 18 mumol/L). Sodium thiosulfate was simultaneously administered intravenously to prevent cisplatin-induced nephrotoxicity. Eight of 26 evaluable patients demonstrated clinical response including seven of 17 (41%) with ovarian cancer refractory to frontline chemotherapy. Systemic toxicity was mild except for nausea and vomiting. Abdominal pain secondary to doxorubicin was the major complication of therapy. We conclude that combination intraperitoneal therapy with cisplatin, cytosine arabinoside, and doxorubicin can be safely administered with objective tumor responses observed in patients with ovarian cancer heavily pretreated and in individuals with other malignancies involving the peritoneal cavity. Doxorubicin-induced local pain limits the ability to administer multiple courses of this treatment regimen.
Brain metastases and testicular tumors: need for aggressive therapy.
Authors: Lester S G , Morphis J G , Hornback N B , Williams S D , Einhorn L H
Published: February 2017

In late 1974, the combination of cisplatin, vinblastine, and bleomycin (PVB) became the standard chemotherapeutic regimen for treatment of disseminated nonseminomatous germ cell testicular tumors (NSGCT) at Indiana University Hospital. A retrospective analysis of the treatment records of all patients with brain metastases from NSGCTs treated at the Indiana University Radiation Oncology Department from 1975 through 1982 was undertaken. These 22 patients were divided into four groups. Group 1 (n = 5) consisted of those patients who presented initially with brain metastases and had no prior systemic treatment. Group 2 (n = 4) were referred to Indiana University after failing systemic therapy other than PVB chemotherapy. Group 3 (n = 5) consisted of those patients who after achieving a complete response with PVB developed a relapse confined to the brain. Group 4 (n = 8) consisted of those patients who were initially treated with PVB and eventually developed progressive disease and brain metastases. The survival by group is 80%, 0%, 60%, and 0%, respectively, with the overall survival for the entire group being 31.8%. All patients currently alive have a range of follow-up of 22 to 96 months from diagnosis and 12 to 83 months from whole brain irradiation (WBRT). Group 1 was treated with PVB +/- doxorubicin plus WBRT. Group 3 was treated with surgical excision, when feasible, followed by WBRT and platinum-containing chemotherapy. Group 2 and 4 were usually treated with palliative intent WBRT. The CNS is a site of sanctuary from PVB. Patients with brain metastases who may achieve a complete response should be treated with curative intent and receive aggressive WBRT (5,000 rad/25 fractions) with concomitant chemotherapy.
Prediction of complete remission in patients with refractory acute leukemia treated with AMSA.
Authors: Estey E H , Keating M J , Smith T L , McCredie K B , Legha S S , Walters R S , Bodey G P , Freireich E J
Published: February 2017

The relation between characteristics known at start of therapy and response in 102 adults with refractory acute leukemia who received 4'-(9 acridinylamino)-methane-sulfon-m-anisidide (AMSA) was examined. Twenty-three (23%) of these patients attained complete remission (CR). Univariate analysis showed that the following characteristics were associated with CR: a fewer number of prior induction and maintenance regimens, a shorter time between latest relapse and AMSA therapy, the presence of Auer rods, a circulating blast cell count of less than 25,000/mm3, a marrow cellularity less than 90%, a ratio of marrow blasts and promyelocytes to more mature myeloid cells (differentiation ratio) less than 15, and a first-course AMSA dose of greater than or equal to 375 mg/m2. Some of these factors were interrelated. Multivariate analysis using logistic regression techniques was carried out to determine which of the above factors added independent prognostic information. This analysis produced a statistical model that related probability of response to the following in order of selection: Auer rod status, first-course dose, differentiation ratio, and absolute circulating blast cell count. Such a model could be useful in identifying patients with high, intermediate, or low probability of response to AMSA. AMSA could then be prescribed only for patients likely to respond while affording other patients alternate salvage programs at an earlier time.
Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.
Authors: Amadori S , Papa G , Avvisati G , Petti M C , Motta M , Salvagnini M , Meloni G , Martelli M , Monarca B , Mandelli F
Published: February 2017

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.
Measuring the quality of life of cancer patients: the Functional Living Index-Cancer: development and validation.
Authors: Schipper H , Clinch J , McMurray A , Levitt M
Published: February 2017

The classical criteria for the evaluation of clinical trials in cancer reflect alterations in physical well-being, but are insensitive to other important factors, such as psychosocial state, sociability, and somatic sensation that may play a critical role in determining the patients' functional response to their illness and its treatment. The Functional Living Index-Cancer is designed for easy, repeated patient self-administration. It is a 22-item questionnaire that has been validated on 837 patients in two cities over a three-year period. Criteria for validity include stability of factor analysis, concurrent validation studies against the Karnofsky, Beck Depression, Spielberger State and Trait Anxiety, and Katz Activities of Daily Living scales, as well as the scaled version of The General Health Questionnaire and The McGill/ Melzack Pain Index. The index is uncontaminated by social desirability issues. The validation studies demonstrate the lack of correlation between traditional measures of patient response and other significant functional factors such as depression and anxiety (r = 0.33), sociability and family interaction, and nausea. These findings elucidate the frequently observed discrepancies between traditional assessments of clinical response and overall functional patient outcome. The index is proposed as an adjunct to clinical trials assessment and may provide additional patient functional information on which to analyse the outcome of clinical trials or offer specific advice to individual patients.
Illusion and reality: practical pitfalls in interpreting clinical trials.
Authors: Glatstein E , Makuch R W
Published: February 2017

This paper has attempted to review for the reader some of the common problem areas in the interpretation of results of cancer treatment. The intention has been to point out potential pitfalls in interpretation so that the reader can comprehend the literature with more insight and criticalness . The plethora of journals and ongoing investigations indicates a greater need for critical understanding on the part of readers. This understanding stretches from the definitions of success and failure used in generating survival curves, to the accumulation and analysis of data and presentation of the results. We hope this paper will help the reader to achieve a greater degree of that understanding.
High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia.
Authors: Hines J D , Oken M M , Mazza J J , Keller A M , Streeter R R , Glick J H
Published: February 2017

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.
The effect of prior cisplatin therapy on the pharmacokinetics of high-dose methotrexate.
Authors: Crom W R , Pratt C B , Green A A , Champion J E , Crom D B , Stewart C F , Evans W E
Published: February 2017

The pharmacokinetics of high-dose methotrexate (MTX, 5-15 g/m2) were evaluated in 11 children and adolescents who had previously received two to eight doses of cisplatin (90 mg/m2) in the treatment of malignant solid tumors. The half-life for disappearance of MTX from serum during the first 24 hours after infusion was determined from serum samples obtained at the end of a six-hour infusion and six, 12, and 24 hours after infusion. These values were compared to a mean half-life of 2.83 (+/- 0.34) hours following 489 courses administered to 71 patients who had not received cisplatin. Stepwise multiple linear regression analysis of patient variables revealed cumulative cisplatin dosage and time from last cisplatin dose as the best predictors of MTX half-life (r2 = 65.4%, p less than 0.001). The best predictors of 24-hour serum concentration were cumulative cisplatin dosage and MTX dosage (r2 = 54.2%, p less than 0.001) in the multiple linear regression model. Patients with delayed MTX clearance received additional leucovorin and experienced no severe toxicity. Patients receiving up to 270 mg/m2 of cisplatin appear to have minimal increases in MTX half-life, while the likelihood of delayed clearance increases in patients who have received 360 mg/m2 or more of cisplatin. All patients who have previously received cisplatin should be treated cautiously with high-dose MTX and prospective pharmacokinetic monitoring should be routinely performed.
Diagnosis and significance of liver metastases in small cell carcinoma of the lung.
Authors: Mulshine J L , Makuch R W , Johnston-Early A , Matthews M J , Carney D N , Ihde D C , Cohen M H , Bates H R , Dunnick N R , Minna J D
Published: February 2017

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.
Clinical utility of terminal deoxynucleotidyl transferase and adenosine deaminase determinations in adult leukemia with a lymphoid phenotype.
Authors: Brusamolino E , Isernia P , Lazzarino M , Scovassi I , Bertazzoni U , Bernasconi C
Published: February 2017

A prospective study was done to assess the clinical utility of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) assays in adult leukemia with a lymphoid phenotype. The study population consisted of 58 patients with adult lymphoblastic leukemia (ALL) at onset, 12 with lymphoblastic lymphoma, 15 with acute unclassifiable leukemia (AUL), and 30 with lymphoid or mixed acute phase of Philadelphia chromosome-positive (Ph' +) chronic myelogenous leukemia (CML). TdT was present in all cases of T-ALL, in 90% of non-T, non-B ALL, and absent in B-ALL; the ADA activity was significantly higher (P less than .01) in T-ALL. TdT was found in 75% of lymphoblastic lymphomas, in 78% of lymphoid, and in 50% of mixed CML transformations; higher ADA activity correlated with TdT positivity in AUL and CML blastic transformations (P less than .001). TdT-positive ALL had a better chance of response to therapy than TdT-negative ALL (P less than 0.01), but survival was not statistically different. TdT was undetectable in the peripheral blood of patients with ALL in complete remission and within the normal range in bone marrow (0.1%-8% of nucleated cells); median ADA activity was as in control subjects. Relapsing ALL patients had TdT and ADA enzymatic activities as before therapy; TdT immunofluorescence test (IF) was positive in 69% of bone marrow and in 100% of CNS relapses. Twenty percent of TdT-positive ALL at onset became TdT-negative in bone marrow at relapse. TdT IF test was instrumental in detecting meningeal leukemia but neither TdT nor ADA could be used as indicators of complete remission or impending relapse because TdT-positive cells were present in normal marrows and wide fluctuations of TdT IF values and of ADA activity were observed in remission.
A randomized study comparing chemotherapy alone with chemotherapy followed by radiotherapy in patients with pathologically staged IIIA Hodgkin's disease.
Authors: Crowther D , Wagstaff J , Deakin D , Todd I , Wilkinson P , Anderson H , Blackledge G , Jones M , Scarffe J H
Published: February 2017

This paper reports the five-year follow-up (range, 1-8 years) of 56 patients with pathologic stage IIIA Hodgkin's disease randomized for chemotherapy alone or chemotherapy followed by radiotherapy to previous areas of disease (26 treated with mustine, vinblastine, procarbazine, and prednisolone [MVPP] alone, 30 with MVPP and radiotherapy). Of the 56 patients 53 (95%) achieved a complete remission with chemotherapy and of these only five (9%) have relapsed; three died of Hodgkin's disease. There was no improvement in relapse-free survival associated with the uses of radiotherapy following chemotherapy but in view of the small numbers of relapses and the excellent results following chemotherapy alone, a significant improvement could not be expected. The use of MVPP alone can be recommended as an alternative therapy for patients with stage IIIA Hodgkin's disease. This avoids both the physical and psychologic morbidity associated with the high relapse rate following extensive primary radiotherapy and the necessity of combined modality treatment for about half these patients. The question of whether radiotherapy should be given to areas of previous bulk following chemotherapy has not yet been answered in this trial which is continuing.
Male breast cancer: a 13-year review of 89 patients.
Authors: Erlichman C , Murphy K C , Elhakim T
Published: February 2017

A retrospective chart review was conducted of men with the diagnosis of carcinoma of the breast seen at this institution between January 1967 and March 1981. Eighty-nine patients were available for analysis. These cases were evaluated to determine whether the natural history of this disease was similar to that of women with carcinoma of the breast and to identify prognostic variables in carcinoma of the male breast. The results of this review would suggest that many similarities exist between breast cancer in women and in men. The most common presenting symptom is a lump, the patterns of recurrence are similar for both men and women, and survival is determined by initial T stage and the presence or absence of nodes. Local postoperative radiotherapy does not influence overall survival in male breast cancer but does decrease the incidence of chest wall recurrence. Survival after recurrence is short and is similar to that observed for women with recurrent carcinoma of the breast. The differences observed in the present series were that the median age at presentation of 63.6 years is somewhat greater than that usually observed in women; no cases of lobular carcinoma were observed; and in the 44 patients who developed recurrences to date, none had evidence of liver metastases as the initial site of recurrence. In most respects the natural history of male breast cancer is similar to that of carcinoma of the breast in women. Since carcinoma of the male breast is a relatively rare malignancy. it is reasonable to recommend management of this disease be based on the greater base of knowledge available for carcinoma of the female breast.
Dexamethasone-induced increase in in vitro clonogenicity of human neoplasms.
Authors: Sloman J C , Murphy M J
Published: February 2017

The addition of the corticosteroid hormone, dexamethasone, to the culture medium results in a significant enhancement of tumor colony growth in the human tumor clonogenic assay. Taking 20 as the mean minimum number of colonies per dish that allows evaluation of 122 cultured tumors, 67 were fully evaluable in the presence of dexamethasone whereas only 34 were evaluable when it was omitted. The addition of dexamethasone significantly (P less than .05) increased the number of evaluable tumors by 23. Tumors cultured included those of the breast, lung, colon, ovary, kidney, and stomach. The response to dexamethasone showed a dose-response relationship over a concentration range typical of corticosteroid receptor-mediated reactions, and it appeared to be steroid specific. Possible mechanisms for this hormone effect are discussed.
Disclosure of information to adult cancer patients: issues and update.
Authors: Goldberg R J
Published: February 2017

Clinicians are regularly faced with decisions regarding disclosure of information to cancer patients. Many of these decisions constitute a dilemma between the physician's paternalistic concern for the patient and the patient's right to know as much as possible. This paper reviews changes in the attitudes of physicians over the last several decades, elaborates on the problems that confront the clinician in the process of disclosure, and reviews the available data concerning the documented impact on the patient from receiving or not receiving information. The arguments both supporting and challenging the paternalistic view are discussed, and the necessity for viewing the disclosure of clinical information as a clinical process is offered.
Lentigo maligna melanoma has no better prognosis than other types of melanoma.
Authors: Koh H K , Michalik E , Sober A J , Lew R A , Day C L , Clark W , Mihm M C , Kopf A W , Blois M S , Fitzpatrick T B
Published: February 2017

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.
Long-term survival of patients with localized diffuse histiocytic lymphoma.
Authors: Vokes E E , Ultmann J E , Golomb H M , Gaynor E R , Ferguson D J , Griem M L , Oleske D
Published: February 2017

From January 1970 to March 1981, localized diffuse histiocytic lymphoma (DHL) was identified in 31 patients by exploratory laparotomy and splenectomy (pathologic stage I, 17 patients; pathologic stage II, 14 patients) at the University of Chicago. The median follow-up time was 72 months. All patients were previously untreated and received radiation therapy as their primary treatment modality. Chemotherapy was administered only at the time of relapse. All but two patients achieved a complete remission (CR) with radiation therapy. The actuarial disease-free survival for patients with stage I disease is 94% at 5 years and 72% at 10 years. For stage II disease, the disease-free survival is 56% at 5 years and 31% at 10 years. The difference in the disease-free survival between stage I and II is statistically significant (P = .02). The survival at 10 years is 70% for stage I disease and 46% for stage II disease. Five patients had documented relapses (four had stage II disease). Only two of those who relapsed achieved a second CR with salvage chemotherapy. Our data show an excellent outcome in patients with pathologic stage I disease, indicating that a high percentage of these cases can be cured with radiotherapy alone. Patients with clinical stage II disease might be served better with chemotherapy.
Creatine kinase BB and beta-2-microglobulin as markers of CNS metastases in patients with small-cell lung cancer.
Authors: Pedersen A G , Bach F W , Nissen M , Bach F
Published: February 2017

Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65 patients analysed for CK-BB, 17 had meningeal carcinomatosis (MC), 26 had parenchymal metastases only, and 22 had no CNS disease. Patients with MC had a significantly higher CK-BB concentration in CSF than did patients belonging to the other two groups (P less than .01). Taking 0.4 U/L (upper limit in patients without CNS disease) as a cut-off point, 15 patients (88%) with MC had elevated CSF concentrations of CK-BB. Patients without CNS metastases had no CSF levels exceeding this value, whereas five patients with multiple CNS metastases did. Receiver operating characteristic (ROC) analysis suggests that CK-BB may be useful in distinguishing MC among patients suspected of having CNS metastases, and CK-BB appears superior to total CK, CSF protein, and CSF lactic dehydrogenase (LDH). In 12 patients with MC at autopsy, CK-BB was, with the above cut-off point, elevated in six patients with a false negative cytology. Of the 73 patients examined for beta-2-m, 18 had MC, 30 had parenchymatous metastases only, and 25 patients had no CNS metastases. The CSF concentrations in the three groups were not significantly different. The median concentrations in the groups were 133 nmol/L, 125 nmol/L, and 107 nmol/L, respectively. The ratios between beta-2-m in CSF and plasma were also not significantly different between the three groups. Thus, the data on CK-BB are promising, and further studies are warranted to see if the usefulness of CK-BB can be more firmly established. By contrast, beta-2-m has no role as a marker of CNS disease secondary to SCLC.
Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer.
Authors: Osoba D , Rusthoven J J , Turnbull K A , Evans W K , Shepherd F A
Published: February 2017

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.
Detorubicin--an active anthracycline in untreated metastatic melanoma.
Authors: Chawla S P , Legha S S , Benjamin R S
Published: February 2017

A phase II study of detorubicin, the semisynthetic 14-diethoxyacetoxy ester of daunorubicin, was conducted in 42 patients with metastatic melanoma. The drug was administered in a dose range of 120 to 180 mg/m2 and repeated at 3-week intervals. One clinical complete remission (soft tissue) and seven partial responses (three visceral and four soft tissue) were observed among the 22 patients who had undergone no prior chemotherapy, a complete and partial response rate of 36%. The duration of response varied from 2 to 27 months with a median of 10 months. There were also four (19%) minor responses (one visceral and three soft tissue). In contrast, among the 20 patients who had undergone prior chemotherapy treatment, only three patients showed a minor response. General toxicities were acceptable and were similar to those of Adriamycin (Adria Laboratories, Columbus, Ohio). Cardiac toxicity was evaluated by cardiac biopsy and radionuclide scan. Cardiac biopsy changes were identical to those observed with Adriamycin and were progressive with cumulative dose. One patient had a high-grade biopsy at a cumulative detorubicin dose of 1,420 mg/m2. Similarly, a trend of decreasing ejection fraction with cumulative dose was noted. Only one patient developed congestive heart failure at a cumulative dose of 1,290 mg/m2, that was well compensated with digoxin and diuretics. In contrast to Adriamycin, detorubicin has shown activity in previously untreated patients with metastatic melanoma.
Adjuvant CMFP versus CMFP plus tamoxifen versus observation alone in postmenopausal, node-positive breast cancer patients: three-year results of an Eastern Cooperative Oncology Group study.
Authors: Taylor S G , Kalish L A , Olson J E , Cummings F , Bennett J M , Falkson G , Tormey D C , Carbone P P
Published: February 2017

After mastectomy, 265 postmenopausal patients with node-positive breast cancer were stratified according to pathologic nodal status and estrogen-receptor (ER) status and randomized to receive either 12 cycles of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or CMFP plus tamoxifen (CMFPT), or observation alone. Patients entered the study between March 1978 and July 1981. Cox regression analysis indicated that, compared to observation alone, chemotherapy (CMFP and CMFPT groups combined) led to a significant reduction in relapses by the end of the first year of study in every examined prognostic subgroup. However, after the first year the relapse-free survival curves of all treatment groups tended to merge, so that by three years 52% of the observation group and 51% of the chemotherapy groups remained disease free. Chemotherapy continued to show a significantly superior relapse-free survival rate for three years only in the subgroup of patients with ER-negative tumors (the subgroup with the largest relapse-free survival advantage at one year). The addition of tamoxifen produced no benefit or harm in any prognostic subcategory examined. ER status was prognostically important for predicting early relapse only in those patients not receiving chemotherapy, due to the greater effectiveness of this chemotherapy to prevent early relapse in the ER-negative subgroup. Treatment has had no early effect on survival. As breast cancer continues to recur even after ten or more years, later relapse patterns may alter these results.
Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study.
Authors: Klaassen D J , MacIntyre J M , Catton G E , Engstrom P F , Moertel C G
Published: February 2017

One hundred ninety-one patients with pathologically confirmed, locally unresectable adenocarcinoma of the stomach (57 patients) and pancreas (91 patients), were randomly allocated to therapy with 5-fluorouracil (5-FU) alone, 600 mg/m2 intravenously (IV) once weekly, or radiation therapy, 4,000 rad, plus adjuvant 5-FU, 600 mg/m2 IV, the first three days of radiotherapy, then follow-up maintenance 5-FU, 600 mg/m2, weekly. Forty-three patients (22%) could not be analyzed because of ineligibility or cancellation, thus 148 patients were evaluable. The median survival time was similar for both treatment programs and for both types of primary carcinoma, and was as follows: gastric primary carcinoma, 5-FU, 9.3 months; 5-FU plus radiotherapy, 8.2 months; pancreatic primary carcinoma, 5-FU, 8.2 months; 5-FU plus radiotherapy, 8.3 months. Substantially more toxicity was experienced by patients treated with the combined modality arm than by those patients receiving 5-FU alone. Severe or worse toxicity experienced by patients with gastric primary carcinoma treated by 5-FU was 19%, and the combined modality arm was 31%. The toxicity experienced by patients with pancreatic primary carcinoma treated with 5-FU was 27%, and the combined modality arm was 51%. Significant prognostic variables included: weight loss in stomach-cancer patients; and performance status, degree of anaplasia, and reduced appetite in pancreas-cancer patients.
Beyond proforma consent for childhood cancer research.
Authors: Leikin S L
Published: February 2017

A critical negotiation is that of obtaining informed consent from those responsible for the child with cancer who is to be involved in clinical research. It requires that the researcher weigh the merits to society of the proposed research trial and the interests of the patient and family. The clinical setting in which agreement to participate is requested and the regulations of the DHHS for such investigations also place special demands on all of those involved. This article is an ethical and psychosocial analysis of informed consent. It is intended to provide pediatric physician-investigators with a better understanding of this complex process to improve their fiduciary relationship with decision makers.
13-cis-Retinoic acid does not increase the true remission rate and the duration of true remission (induced by cytotoxic chemotherapy) in patients with chronic phase chronic myelogenous leukemia.
Authors: Arlin Z A , Mertelsmann R , Berman E , Gee T , Kurland E , Chaganti R S , Jhanwar S C , Moore M A , Clarkson B D
Published: February 2017

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.
Intraocular retinoblastoma group V: an analysis of prognostic factors.
Authors: Rubin C M , Robison L L , Cameron J D , Woods W G , Nesbit M E , Krivit W , Kim T H , Letson R D , Ramsay N K
Published: February 2017

A retrospective analysis of the University of Minnesota (Minneapolis) experience with retinoblastoma is presented. Seventy-five patients were diagnosed with retinoblastoma between 1958 and 1983, of which 53 (71%) had at least one Reese-Ellsworth group V eye. Nineteen group V patients and one group II patient developed extraocular disease recurrence. The cumulative actuarial rate of recurrence at 12 years was 36% for patients with group V disease. The median time from diagnosis to recurrence for unilateral patients was seven months and for bilateral patients 28 months (P = .001). Patients developing extraocular disease had a 10-year actuarial survival rate postrecurrence of 34%. The four long-term survivors of extraocular recurrences had had isolated orbital or local soft tissue recurrences only. Features of group V patients associated with extraocular recurrences were identified by univariate life table analyses. Clinical poor-risk factors included the nongenetic form of the disease (P = .03) and male sex (P = .02). Pathologic poor risk factors included rubeosis (P = .01), undifferentiated histology (P = .03), large tumor size (P = .05), and intraocular extension to the anterior segment (P = .02), retinal pigment epithelium (P = .03), choroid (P less than .001), and optic nerve beyond the lamina cribrosa (P = .02). Treatment-associated poor-risk factors included an optic nerve length of less than 5 mm removed at enucleation (P = .003). Multivariate life table analyses demonstrated the following parameters to be independent poor-prognostic factors: optic nerve length of less than 5 mm removed at enucleation (P = .001), optic nerve involvement (P = .004), and large tumor size (P = .01). These results will help to identify patients with retinoblastoma who are at greatest risk for extraocular recurrence.
Phase I trial of N-methylformamide (NMF, NSC 3051).
Authors: O'Dwyer P J , Donehower M , Sigman L M , Fortner C L , Aisner J , Van Echo D A
Published: February 2017

N-methylformamide (NMF) is a polar-planar solvent with both cytotoxic and differentiating activity in preclinical models; it also acts as a radiosensitizer. We treated 17 patients with 18 courses of NMF on a schedule of six weekly doses, administered on a rapid intravenous infusion, which were escalated from 875 to 2,000 mg/m2/wk. The predominant toxicity was a dose-related syndrome of fatigue, malaise, nausea, and anorexia, which was reflected by a decrease in performance status (Karnofsky) of greater than or equal to 20% in six of ten patients who received doses greater than or equal to 1,500 mg/m2/wk. Other gastrointestinal toxicities included moderate vomiting and mild diarrhea. Reversible increase of liver enzymes occurred in six of ten patients at doses greater than or equal to 1,500 mg/m2/wk. The maximum tolerated dose on this schedule is 1,500 mg/m2/wk; the dose recommended for phase II studies is 1,125 mg/m2/wk. Future studies of this regimen in a combined modality setting are planned.
Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract.
Authors: Kalra J , Cortes E , Chen S , Krumholz B , Rovinsky J J , Molho L , Seltzer V , Papantoniou P , Lee J Y
Published: February 2017

Fifteen patients with advanced or recurrent squamous-cell carcinoma of the cervix, vulva, vagina, and urethra were treated with simultaneous combination chemotherapy (5-fluorouracil infusion and mitomycin C) and radiotherapy (3,000 rad for a period of three weeks). Three to four weeks after completion of radiotherapy, 13 of 15 patients achieved partial or complete tumor shrinkage. Nine of 15 patients are alive, eight of whom (at a median follow-up time of 24 months) have no evidence of disease. The longest survival time was 45 + months. There was minimal toxicity associated with this therapy. The results of this pilot study suggest that the simultaneous administration of radiation and chemotherapy is an effective method of treatment of advanced female genital tract carcinoma.
Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report.
Authors: Quesada J R , Swanson D A , Gutterman J U
Published: February 2017

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study.
Authors: Veronesi A , Zagonel V , Tirelli U , Galligioni E , Tumolo S , Barzan L , Lorenzini M , Comoretto R , Grigoletto E
Published: February 2017

From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low-dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial.