bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone marrow infiltration patterns and their prognostic significance in chronic lymphocytic leukemia: correlations with clinical, immunologic, phenotypic, and cytogenetic data.
Authors: Han T , Barcos M , Emrich L , Ozer H , Gajera R , Gomez G A , Reese P A , Minowada J , Bloom M L , Sadamori N
Published: February 2017

Bone marrow biopsies were prospectively performed on 75 patients with chronic lymphocytic leukemia (CLL). There was a highly significant relationship (p less than 0.002) between clinical stages and bone marrow infiltration patterns. Ten (50%) of 20 patients with diffuse patterns died; the estimated median survival time for these patients was 87 months. In contrast, only six (11%) of 55 patients with nondiffuse patterns died; the estimated median survival time for these patients could not be computed. When both clinical stage and infiltration pattern were evaluated for survival, a highly significant association between clinical stage and survival time was still observed (p less than 0.003) whereas bone marrow infiltration pattern was no longer significant. A significant association was also observed between bone marrow infiltration patterns and absolute lymphocyte counts (p less than 0.0005), Fc-receptor-positive cells (p less than 0.002), 3H-thymidine uptake of leukocytes (p less than 0.01), serum alkaline phosphatase levels (p less than 0.05), monoclonal urinary-free light chain status (p less than 0.05), and cytogenetics of leukemic cells (p less than 0.05). These observations lead to the conclusion that in an overall prognostic evaluation of patients with CLL, although bone marrow histopathology may have no additional value over a well-established clinical staging system, as a whole, it may be of clinically predictive value in disease progression of patients with stage I and II.
A randomized trial of metoclopramide and a combination of dexamethasone and lorazepam for prevention of chemotherapy-induced vomiting.
Authors: Gagen M , Gochnour D , Young D , Gaginella T , Neidhart J
Published: February 2017

In a randomized, crossover design the antiemetic activity of one of the most active single agents, metoclopramide was compared with a combination of dexamethasone and lorazepam. Both regimens were effective, but dexamethasone-lorazepam was significantly better than metoclopramide in preventing (26% versus 13%) or limiting (44% versus 23%) vomiting. Although side effects were more frequent with lorazepam-dexamethasone, the patients generally judged them desirable and overall patient preference was strong (70% versus 12%) for the lorazepam-dexamethasone combination. Patients required supervision and assistance due to lorazepam-induced drowsiness.
Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience.
Authors: Tester W J , Kinsella T J , Waller B , Makuch R W , Kelley P A , Glatstein E , DeVita V T
Published: February 2017

The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease. Eight cases of acute nonlymphocyctic leukemia, one case of chronic myeloid leukemia, three cases of non-Hodgkin's lymphoma, three cases of sarcoma, and 19 other tumors were identified. The ten-year estimated risk of leukemia by treatment was the following: radiotherapy only (0), chemotherapy only (0.02), initial combined radiotherapy-chemotherapy (0.06), and salvage combined radiotherapy-chemotherapy (0.09). The ten-year estimated risk of solid tumors was 0.07 overall, with all treatment groups associated with similar risks. Unlike some other reports, a greater risk of leukemia in patients who began treatment for Hodgkin's disease at age 40 or older was not found. However, a positive association was noted between increasing risk of solid tumors and increasing patient age.
Combined therapy for stage III-IV head and neck cancer: preliminary results.
Authors: Krasnow S H , Cohen M H , Johnston-Early A , Citron M L , Fossieck B E , Mauk C M , Yenson A , Banda F P , Lunzer S , deFries H O
Published: February 2017

As part of a combined modality treatment program using chemotherapy, surgery, and/or radiotherapy, 25 patients with previously untreated stage III or IV head and neck cancer received initial combination chemotherapy. Pathologically confirmed complete remission was noted in nine patients (36%). The overall objective major response rate (with all patients included in analysis) was 68%. The chemotherapy regimen included bleomycin, cisplatin, vinblastine, methotrexate, and 5-fluorouracil. A novel concept of drug scheduling was used, based on chemotherapy-induced improvement in RBC deformability. The underlying concept is that improved RBC deformability results in improved capillary blood flow and thereby, increased drug delivery to tumor cells. Treatment resulted in moderate hematologic and renal toxicity with no treatment-related deaths. This exceptionally high, pathologically confirmed complete response rate will hopefully provide a mechanism by which combined modality therapy can adequately be tested for its ability to prolong survival of patients with advanced head and neck cancer.
Follicular large cell lymphoma: analysis and prognostic factors in 62 patients.
Authors: Kantarjian H M , McLaughlin P , Fuller L M , Dixon D O , Osborne B M , Cabanillas F F
Published: February 2017

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.
Lymphocyte surface markers in orbital lymphoid neoplasms.
Authors: Harmon D C , Aisenberg A C , Harris N L , Dallow R L , Linggood R M , Wilkes B M
Published: February 2017

Since the malignant nature of many orbital lymphoid infiltrates is difficult to assess from pathologic examination alone, over the past four years lymphocyte surface marker studies have been added to the evaluation of 23 such cases. Only 10 of the 23 could be confidently classified as malignant lymphoma by histology alone. However, monoclonal surface immunoglobulin was found in 15, supporting the pathologic diagnosis of malignancy in eight and adding seven that could not have been diagnosed otherwise. Clinical evaluation, including a median follow-up of 18 months, revealed manifestations of systemic lymphoma in six of those 15; two had been diagnosed only by surface markers. In contrast, only one of eight cases lacking monoclonal surface immunoglobulin exhibited clinical evidence of malignancy (that case was also indeterminate by histologic criteria). The addition of surface marker analysis permits more accurate diagnosis of orbital lymphoma than is possible from pathologic study alone. This technique can suggest the subtype of lymphoma.
Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.
Authors: Creagan E T , Ahmann D L , Green S J , Long H J , Frytak S , O'Fallon J R , Itri L M
Published: February 2017

Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen.
Influence of measurement error on assessment of response to anticancer chemotherapy: proposal for new criteria of tumor response.
Authors: Warr D , McKinney S , Tannock I
Published: February 2017

The decision to use a given type of chemotherapy to treat cancer patients is often based on the prior demonstration that a proportion of similar patients has "responded" in a clinical trial. Most responses are recorded as a partial shrinkage of tumor, defined usually as a greater than 50% shrinkage of the sum of cross-sectional areas of index lesions for at least one month. The errors in categorization of response have been estimated by comparing measurements of several physicians on real or simulated malignant lesions. False categorization of partial response based on a comparison of two measurements of the same lesion was 1.3% and 12.6% for large and small simulated nodules, respectively, 13.1% for malignant neck nodes, and 0.8% for metastatic lung nodules. Partial response for hepatic lesions has been defined by a 50% or 30% decrease in liver span below the costal margin; these definitions led to a false categorization of partial response of 8.5% and 18.4%, respectively. Larger errors are evident when using the current definition of disease progression that requires only a 25% increase in area. False categorization of response is increased by comparing any of serial measurements with the initial lesions, as is usually done clinically. Many published trials have used criteria for response that are subject to large errors; an uncritical interpretation of their results may lead to inappropriate treatment of patients. Based on the results, new criteria for evaluating tumor response are proposed.
A controlled trial of the effect of 4-hydroxypyrazolopyrimidine (allopurinol) on the toxicity of a single bolus dose of 5-fluorouracil.
Authors: Woolley P V , Ayoob M J , Smith F P , Lokey J L , DeGreen P , Marantz A , Schein P S
Published: February 2017

We have evaluated, in a controlled study, the modification of the toxicity of a single bolus dose of 5-fluorouracil (5-FU) by allopurinol. Patients first received a single dose of 5-FU and were monitored for toxicity. If a measurable nadir in WBC or platelet count occurred, then the same dose of 5-FU was repeated with concurrent allopurinol, given for four consecutive days at an initial dose of 300 mg twice daily, starting the day before the administration of 5-FU. With this schedule, each evaluable patient received courses of 5-FU with and without allopurinol that could be compared for toxicity. Twenty patients received initial 5-FU doses of either 1,200 mg/m2 or 1,500 mg/m2 and later had the same dose repeated with allopurinol. Nineteen of these patients had a higher WBC count with allopurinol than without it. In several patients who received a further course of 5-FU with 900-mg/d allopurinol, the WBC count was yet higher than with 600-mg/d allopurinol. The myelosuppression produced by 5-FU was characterized by a decrease in granulocyte levels that was much greater than the decrease in lymphocyte levels, and the result of allopurinol treatment was to attenuate this effort on granulocytes. In a second part of the trial, the goal was to establish the maximum tolerated dose of 5-FU given with concurrent allopurinol. In this part of the study, all patients entered were given 5-FU, usually 1,200 mg/m2, with allopurinol, usually 600 mg/d for four days. Escalations of one or the other drugs were made on subsequent treatments. The data for 22 patients showed that 1,800 mg/m2 of 5-FU was well tolerated if given with 600 to 1,200 mg of allopurinol per day, and that the WBC count nadirs were no more severe than those of 1,200-mg/m2 5-FU without allopurinol. Neurotoxicity became limiting in some patients treated at these higher doses. We conclude that allopurinol given in the proper dose and schedule can diminish the granulocytopenia produced by bolus doses of 5-FU, thereby allowing a 50% increase in the maximal tolerated dose of 5-FU.
Secondary malignancies of the penis and epididymis: a case report and review of the literature.
Authors: Powell B L , Craig J B , Muss H B
Published: February 2017

A patient with carcinoma of the colon developed metastases to the penis and right epididymis. These two organs are rare locations for metastases and the concurrent involvement of both sites has not been previously described. Our patient and the results of a literature review are presented. Two hundred eighteen cases of penile and 37 separate cases of epididymal metastases were identified. The genitourinary and gastrointestinal tracts were the predominant sites of the primary malignancies. Presenting symptoms, the interval between diagnoses of the primary and metastatic lesions, and the therapy of the penile/epididymal deposits varied greatly. Surgical excision is the major mode of therapy; radiotherapy, chemotherapy, or hormonal therapy may be beneficial in selected cases. Survival among these patients is poor due to the presence in most patients of widespread metastases in addition to their genital lesions. However, instances of prolonged survival are noted in both groups. Patient characteristics and possible mechanisms of metastatic spread to the genitals are discussed.
Stage IV diffuse large-cell lymphoma: a long-term analysis.
Authors: Jagannath S , Velasquez W S , Tucker S L , Manning J T , McLaughlin P , Fuller L M
Published: February 2017

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.
Cerebrospinal fluid vasopressin as a marker of central nervous system metastases from small-cell bronchogenic carcinoma.
Authors: Pedersen A G , Hammer M , Hansen M , Sørensen P S
Published: February 2017

Vasopressin (ADH) was measured in CSF and plasma in 75 evaluable patients with known or suspected CNS metastases from small-cell bronchogenic carcinoma (SCBC), and in 66 control patients having neither malignant disease nor organic CNS disease. The presence of CNS metastases was confirmed or excluded on the basis of computed tomographic scans, neurologic examination, and autopsy. Twenty-four of the 75 patients had no CNS metastases. Ten of the 51 patients with CNS metastases had leptomeningeal carcinomatosis (MC). CSF-ADH was significantly increased in patients with MC (P less than .05), but not in patients having exclusively parenchymatous CNS metastases. Taking 2 pg/mL (95th percentile of control patients) as the upper limit of normal, 15 SCBC patients had elevated CSF-ADH, including 12 patients with CNS metastases and six patients with MC. The CSF-ADH to plasma ADH ratio was significantly increased in patients with CNS metastases (P less than .05). Patients without CNS metastases had a ratio less than or equal to 0.8 whereas the ratio was greater than 0.8, in 21 of the 51 patients with CNS metastases. The positive and negative predictive values with 95% confidence limits were 84% to 100% and 31% to 59%, respectively. Patients with inappropriate secretion of ADH (SIADH) constituted a significantly greater proportion of patients with elevated CSF-ADH than of patients with normal CSF-ADH levels (P less than .05). In addition, patients with SIADH constituted a significantly greater proportion of patients with MC than of patients with parenchymatous metastases (P less than .05). The diagnostic application of these findings is limited because of the large number of false-negative results, but it may prove to be of value in conjunction with the measurement of other tumor markers.
Chemotherapy for metastatic non-small-cell bronchogenic carcinoma: EST 2575, generation V--a randomized comparison of four cisplatin-containing regimens.
Authors: Ruckdeschel J C , Finkelstein D M , Mason B A , Creech R H
Published: February 2017

Between December 1979, and October 1981, the Eastern Cooperative Oncology Group (ECOG) compared four cisplatin-containing regimens in the treatment of patients with metastatic non-small-cell bronchogenic carcinoma (NSCBC). CBP (cyclophosphamide, bleomycin, and cisplatin) and AFP (doxorubicin, 5-fluorouracil, and cisplatin) had shown activity in generation II of this study (EST 2575). These were compared to MVP (mitomycin C, vinblastine, and cisplatin) and CAP (cyclophosphamide, doxorubicin, and cisplatin) which were reported efficacious in single institution studies. A total of 479 previously untreated patients with metastatic NSCBC (ECOG performance status 0, 1, or 2) were entered, and of these, 432 (90%) were evaluable. Although MVP resulted in a higher response rate (5 complete responses [CRs], 22 partial responses [PRs], 26% overall) than CBP (4 CRs, 18 PRs, 20% overall), AFP (0 CRs, 18 PRs, 17% overall), or CAP (1 CR, 23 PRs, 23% overall), the difference was not significant. Survival by treatment did not differ significantly. There were 45 life-threatening and six lethal complications of therapy. Although each of the above regimens offers a modest chance of inducing greater than 50% tumor shrinkage (17% to 26%, 21% overall) the effect that these responses have an overall median survival (21.6 to 23.7 weeks, 22.9 weeks overall) is unclear.
Radiotherapy as initial treatment for bulky stage II testicular seminomas.
Authors: Smalley S R , Evans R G , Richardson R L , Farrow G M , Earle J D
Published: February 2017

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.
Intraductal carcinoma of the breast: results of treatment with excisional biopsy and irradiation.
Authors: Recht A , Danoff B S , Solin L J , Schnitt S , Connolly J , Botnick L , Goldberg I , Goodman R L , Harris J R
Published: February 2017

Between 1976 and 1983, 40 women with intraductal carcinoma of the breast without invasion underwent excisional biopsy and irradiation as an alternative to mastectomy. The median age was 53 years (range, 28 to 77 years) and the median follow-up time since initiation of radiation was 44 months (range, 14 to 97 months). Twenty-seven patients presented with a palpable mass; in 13 patients the tumor was detected only by mammography. A limited axillary dissection was performed in 13 patients, and all lymph nodes removed were negative. Treatment was administered to the breast and adjacent chest wall to a dose of 4,600 to 5,000 rad, with 26 patients also receiving a boost dose of 1,000 to 2,000 rad to the site of the primary. Four patients have developed a recurrence in the treated breast, at 17, 19, 35, and 63 months after the beginning of radiation therapy. The 5-year actuarial rate of local recurrence is 10%. Three of the recurrences were in those four patients who presented with a nipple discharge and a central primary. In two cases, the recurrence consisted of only intraductal carcinoma; in the other two, both intraductal and invasive cancer were found. All four patients with recurrence underwent mastectomy and are well without evidence of distant metastases at 1, 12, 15, and 15 months since mastectomy. Cosmetic results were excellent. No patient has developed distant metastases. Since the number of patients treated is small and the period of follow-up is short, one must be cautious in the interpretation of these results. Nonetheless, the treatment of intraductal carcinoma of the breast by excision and irradiation appears to give acceptable local control and excellent survival when suitable precautions of patient selection and evaluation are taken.
High-dose cisplatin administration without hypertonic saline: observation of disabling neurotoxicity.
Authors: Legha S S , Dimery I W
Published: February 2017

Nephrotoxicity of cisplatin can be ameliorated with intravenous (IV) hydration and forced diuresis with mannitol. Cisplatin has recently been used with hypertonic saline which allows administration of higher doses amounting to 40 mg/m2/d for 5 days, without significant nephrotoxicity. In this report we describe our experience with administration of cisplatin in a dose range of 30 to 40 mg/m2/d for 5 days, administered with IV hydration alone. Thirteen patients with recurrent carcinoma of the head and neck region were treated with high-dose cisplatin along with 5-fluorouracil (5-FU) used as a continuous infusion. Eight patients received a total of 21 courses of cisplatin with the higher dose range (40 mg/m2 for 5 days) and the remainder received 11 courses with the lower dose range. The renal toxicity was minimal but the myelo-suppression was intense, frequently requiring hospitalization for the treatment of infections associated with neutropenia. Furthermore, we encountered severe peripheral neuropathy in five patients, four of whom developed major difficulties with ambulation. Six patients achieved objective regression of their tumor, two had minor response, and five failed to respond to chemotherapy. The study was terminated because of serious nonrenal toxicity from the high-dose cisplatin. Based on our limited experience, we believe that IV hydration alone, without the use of hypertonic saline, allows administration of high-dose cisplatin without significant nephrotoxicity. However, cisplatin used in a dose schedule of 40 mg/m2 for 5 days for more than three courses resulted in a disabling form of peripheral neuropathy.
Plasma cell acid phosphatase activity as prognostic factor in multiple myeloma: relationship to the thymidine-labeling index.
Authors: Boccadoro M , Gallamini A , Fruttero A , Gavarotti P , Redoglia V , Buffa F , Ruá S , Pileri A
Published: February 2017

Plasma cell acid phosphatase (AP) activity and thymidine labeling index (LI%) were evaluated concomitantly in 52 patients with monoclonal gammopathies. AP score, percentage of AP positive plasma cells, and LI% were significantly higher in 26 patients with multiple myeloma (MM) at the time of diagnosis than in 11 monoclonal gammopathy of undetermined significance (MGUS) and eight smoldering myeloma (SM) patients. LI% had the highest statistical correlation with disease status. A 1% cutoff could clearly separate the patients with progressive MM compared to those with stable disease (SM-MGUS) (P less than .001). There was a significant overall correlation between the AP score and LI% (P less than .005). Since LI% is a recognized powerful prognostic factor, this correlation suggests that the AP score can also be a reliable test predicting patient survival duration. In addition, we identified a subgroup of IgG MM patients with very high tumor mass who had a low LI% but a high AP score. This was associated with very poor patient survival and indicated the discrete prognostic importance of AP score in this subgroup with low LI%. Thus, both the LI% and AP score can be recommended as helpful clinical tests in patients with monoclonal gammopathies.
Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients.
Authors: Dedhar S , Hartley D , Fitz-Gibbons D , Phillips G , Goldie J H
Published: February 2017

Dihydrofolate reductase activity was found to be highly heterogeneous in terms of its specific activity and methotrexate sensitivity in the blast cells of patients with acute myelogenous leukemia. None of the patients had previously been treated with methotrexate (MTX). The blast cells of four of 12 patients studied contained methotrexate-insensitive forms of dihydrofolate reductase, and the blast cells of three (distinct from the four mentioned previously) of the 12 had significantly higher dihydrofolate reductase activities than the rest. The presence of MTX-insensitive dihydrofolate reductases and high levels of enzyme activity represent intrinsic mechanisms of resistance and may explain the apparent clinical resistance of acute myelogenous leukemia to methotrexate.
Iodine 131 antiferritin, a new treatment modality in hepatoma: a Radiation Therapy Oncology Group study.
Authors: Order S E , Stillwagon G B , Klein J L , Leichner P K , Siegelman S S , Fishman E K , Ettinger D S , Haulk T , Kopher K , Finney K
Published: February 2017

One hundred five patients with hepatoma were treated with iodine 131 antiferritin in three sequential protocols in phase 1-2 trials. Therapy began in all trials with external beam irradiation and chemotherapy. The dosimetric results with 131I antiferritin indicated that 30 mCi (8 to 10 mCi/mg immunoglobulin G [IgG]) was sufficient to saturate the tumor. Tumor-effective half-life of the radioactive antibody was 3 to 5 days and was dependent on the species of animal from which the antibody was derived. This led to a 30 mCi on day 0 and 20 mCi on day 5 treatment schedule. Toxicity was predominantly thrombocytopenia. Due to clinical remission, cyclic therapy was next developed with antibodies from different species of animals. Rabbit, pig, monkey, and bovine antibodies were determined to produce the longest tumor-effective half-life and therefore the highest dose of radiation. Integration of 15 mg doxorubicin and 500 mg 5-fluorouracil (5-FU) with 131I antiferritin was accomplished next. Remission to external beam radiation was evaluated by computed tomography (CT) scan tumor volume computations that indicated that 22% of the patients had a partial remission (PR) from initial presentation to 1 month following external irradiation and chemotherapy. From the time of radioactive antibody administration, 48% of the patients (7% complete response [CR] and 41% PR) achieved remission to 131I antiferritin. Of 79 patients evaluated by CT scan tumor volumetrics 50% of the patients (7% CR and 43% PR) remitted to the entire treatment regimen. Patients not previously treated and without metastasis who were alpha fetoprotein positive (AFP+) had a 5-month median survival compared with AFP- median survival of 10 1/2 months. There were four CRs with one being 3 years and 6 months. The longest PR was 5 years and 8 months. These studies have demonstrated the toxicity and therapeutic activity of 131I antiferritin and the emerging role of radiolabelled antibody in cancer therapy.
Pediatric Hodgkin's disease in India.
Authors: Dinshaw K , Pande S , Advani S , Ramakrishnan G , Nair C , Talvalkar G , Rao D N , Notani P , Rao R , Desai P
Published: February 2017

Twenty-one percent of all Hodgkin's disease in India was seen in the pediatric age groups at the Tata Memorial Hospital (Bombay, India). From 1975 to 1982, 151 cases of children were reviewed. The youngest presentation was at 3 years in three patients, with a marked male: female ratio of 5.5:1. Twenty-six patients were previously treated before referral while the remaining 125 cases were investigated and treated according to the prevalent protocols in 1975 to 1978 and 1979 to 1982. Clinical staging revealed 54% of patients in stages I and II with symptoms in 20%, and 46% of patients in stages III and IV with symptoms in 67%. Staging laparotomy was performed in 27 patients, with a total changes of staging in 17 children (63%). The mixed cell types (46%) and lymphocytic predominant types (31%) were the most common histologic presentations. Nine percent nodular sclerosis and 9% lymphocytic-depleted varieties were also observed. Five percent of all cases were not classifiable. Minimum adequate treatment was completed in 87 cases. Comparisons were made between the treatments administered to 40 patients during the initial period 1975 to 1978 when individualized treatment was administered, and the later 47 patients during the 1979 to 1982 period, when chemotherapy was the mainstay of treatment with involved field radiation.
Clinical Pharmacokinetics of High-Dose Metoclopramide in Cancer Patients Receiving Cisplatin Therapy
Authors: McDermed Jonathan E. , Cohen Jordan L. , Joseph Corrine , Strum Stephen B.
Published: February 2017

In the article by McDermed et al "Clinical Pharmacokinetics of High-Dose Metoclopramide in Cancer Patients Receiving Cisplatin Therapy" (Journal of Clinical Oncology 3:1400–1408, 1985), an error was made in the second column on page 1401 that altered the meaning of an equation. The correct equation appears below.

Please see the PDF for Equation.
Lung cancer in Hodgkin's disease: association with previous radiotherapy.
Authors: List A F , Doll D C , Greco F A
Published: February 2017

Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that we observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation.
Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate.
Authors: Scher H I , Yagoda A , Ahmed T , Watson R C
Published: February 2017

Methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis, was administered to 35 patients with hormone-resistant advanced adenocarcinoma of the prostate in doses of 500 or 600 mg/m2 per week intravenously. Of 31 patients with bidimensional measurable soft-tissue lesions, 25 had an adequate trial, defined as four or more doses. Six (24%; 95% confidence limits, 8% to 32%) patients achieved a partial remission (greater than or equal to 50% reduction in tumor size) in soft-tissue disease. Response was noted to start after one to two doses and persisted for a median of three months (range, 1 to 4 months). Toxicity was tolerable, and significant myelosuppression was not observed. The lack of response in osseous metastases may be secondary to the short duration of remission or to the presence or inducibility of the enzyme ornithine decarboxylase in bone. Since some animal prostatic cancer tumor models are sensitive to cytotoxic drugs that produce polyamine inhibition, clinical trials of MGBG combined with other inhibitors of the polyamine pathway should be explored.
Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.
Authors: Rios A , Mansell P W , Newell G R , Reuben J M , Hersh E M , Gutterman J U
Published: February 2017

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.
Neoplastic fever responds to the treatment of an adequate dose of naproxen.
Authors: Chang J C , Gross H M
Published: February 2017

Twenty-one patients with neoplastic fever due to malignancy were treated with naproxen. A prompt and complete lysis of fever was obtained in 20 patients within 12 hours when an adequate dose of naproxen was given, and a sustained normal temperature was maintained in all responding patients while receiving naproxen except for one in whom a low grade fever recurred. Lysis of fever usually was followed by excessive sweating and subjective symptomatic improvement. However, when naproxen was discontinued in ten patients, febrile state to the pretreatment level recurred in seven patients within three days. This observation suggests naproxen has a definite and effective antipyretic activity against neoplastic fever although it may recur as the drug is discontinued. Naproxen may be a useful adjunctive agent in patients with neoplastic fever for a short-term symptomatic relief.
Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: results of a Southeastern Cancer Study Group trial.
Authors: Hainsworth J D , Williams S D , Einhorn L H , Birch R , Greco F A
Published: February 2017

Between July 1979 and May 1982, we treated 45 male patients with refractory germinal neoplasms. All patients had previously received intensive cisplatin-containing combination chemotherapy regimens. Patients received salvage chemotherapy with VP-16 and cisplatin +/- bleomycin +/- doxorubicin. Of 44 evaluable patients, 19 (43%) achieved complete remissions with salvage chemotherapy, 12 (27%) had partial remissions, and nine (21%) had no response. Four patients (9%) were not evaluable for response due to early death or noncompliance but are considered treatment failures. Ten patients (23%) remain alive and continuously disease free 20 to 39 months (median, 29 months) after completion of therapy. Hematologic toxicity was severe, with one death related to sepsis. Bleomycin-induced pulmonary fibrosis occurred in 17 patients with two fatalities. The addition of bleomycin and/or doxorubicin to this regimen increases toxicity and probably does not improve treatment results. Salvage chemotherapy with VP-16 and cisplatin offers potentially curative therapy to men with resistant germinal tumors.
Drug-induced antibodies during 2-N-methyl-9-hydroxyellipticinium acetate (NSC-264137) treatment: schedule dependency and relationship to hemolysis.
Authors: Mondesir J M , Bidart J M , Goodman A , Alberici G F , Caille P , Troalen F , Rouesse J , Bohuon C , Gralla R J , Einzig A I
Published: February 2017

Drug-dependent antibodies were investigated in patients treated with elliptinium acetate, a cytostatic drug with activity in advanced breast cancer. Retrospective analysis of 83 patients, receiving weekly intravenous elliptinium, showed a high incidence of anti-elliptinium antibodies (20%). Hemolysis occurred among antibody-positive patients, apparently related to the antibody titer. The predictability of anti-elliptinium antibodies for hemolysis and the schedule dependency of antibody development was examined prospectively. Among 42 patients treated weekly for at least three courses, 40% developed antibodies. Of 30 patients receiving elliptinium daily for three days every three weeks, none developed either antibodies or hemolysis. Only antibody positive patients, with titers greater than or equal to 32 were at risk for hemolysis. The possible mechanisms are discussed.
Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.
Authors: Ezdinli E Z , Anderson J R , Melvin F , Glick J H , Davis T E , O'Connell M J
Published: February 2017

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.
Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia.
Authors: Abromowitch M , Bowman W P , Ochs J , Rivera G
Published: February 2017

Fifty children with acute lymphoblastic leukemia (ALL) in first to fifth relapse were treated with a three-drug reinduction regimen consisting of prednisone (40 mg/m2/d for seven days), vincristine (1.5 mg/m2 on day 1) and etoposide (VP-16, 250 mg/m2 on days 1 through 3). The intent was to assess the efficacy of VP-16 in an otherwise conventional reinduction plan, especially in patients who had previously received teniposide (VM-26), the close congener of VP-16. Among the 46 patients who received at least two courses of the therapy, 16 (0.34) achieved complete remission. Seven others showed improvement in their bone marrow status. Each child had been heavily pretreated with prednisone and vincristine, and 14 had received VM-26. That seven patients judged to be clinically resistant to VM-26 had complete responses to prednisone-vincristine-VP-16 indicates that prior treatment with one podophyllotoxin derivative does not preclude responses to the other. We are uncertain about the pharmacologic basis of these results but suggest that the increased dosage and more frequent administration of VP-16, relative to that of VM-26, was sufficient to overcome apparent resistance to the latter compound. Remission durations ranged from one to eight months (median, four months), emphasizing the need to devise more effective continuation therapy, including investigational agents such as the epipodophyllotoxins.
Criteria of tumor response used in clinical trials of chemotherapy.
Authors: Tonkin K , Tritchler D , Tannock I
Published: February 2017

We have studied 61 published reports of trials of cancer chemotherapy to evaluate the criteria for tumor response that were used and the adequacy of their description in the publication. Our sample comprised recent articles published in three major journals that addressed the influence of chemotherapy on patients with recurrent or metastatic colorectal cancer, non-small cell lung cancer, and head and neck cancer. Incomplete information was sought through a questionnaire mailed to the senior author of each paper, and 48 of them responded. We conclude that: no article contained all of the information required to define precisely criteria for tumor responses; criteria for tumor response are variable; and differences in response criteria contribute to the wide variation in reported rates of tumor response. Meaningful intercomparison of clinical trials will require the establishment of uniform criteria for assessing and reporting the response of tumors to chemotherapy.
Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate?
Authors: Tannock I F
Published: February 2017

Most patients with metastatic carcinoma of the prostate have osteoblastic bone metastases and nonmeasurable pelvic disease. These features cause patients to be at high risk for myelosuppression after cytotoxic chemotherapy and make it difficult to evaluate response to treatment. A critical review of larger trials that have sought to assess the role of chemotherapy in treatment of carcinoma of the prostate leads to the following conclusions: (1) Although the aim of treatment is palliation, most trials have tried to evaluate tumor response rather than the more appropriate endpoints of quality and quantity of survival for all treated patients. (2) Criteria that have been used for tumor response are variable and contain large inherent errors; most patients who are labeled as "responders" are described as being "objectively stable," but this category may be a manifestation of slowly progressive disease rather than a response to treatment. (3) There is no evidence that chemotherapy causes a meaningful prolongation of survival. (4) Chemotherapy adds considerable toxicity, and reported trials have not adequately assessed its overall impact on quality of life. Because of these factors there is little evidence that chemotherapy provides palliation for patients with prostatic carcinoma, and it should not be regarded as part of standard management. Selected patients who are symptomatic and no longer responding to hormones may be considered for trials of chemotherapy. Future trials should randomize patients to chemotherapy or supportive care, with assessment of quality and quantity of survival for all randomized patients by an observer who is unaware of the treatment.
Sequential high-dose cytosine arabinoside-asparaginase treatment in advanced childhood leukemia.
Authors: Wells R J , Feusner J , Devney R , Woods W G , Provisor A J , Cairo M S , Odom L F , Nachman J , Jones G R , Ettinger L J
Published: February 2017

Sequential high-dose cytosine arabinoside (ara-C) and asparaginase were given to 41 children age six months to 21 years of age with advanced leukemia. Ten of 22 patients with acute lymphocytic leukemia (ALL) and eight of 19 patients with acute nonlymphocytic leukemia (ANLL) obtained complete remissions. The most significant toxicity seen was infection in 22 patients. In addition, patients given intrathecal chemotherapy within 24 hours of ara-C developed neurologic toxicity. The high response rate seen in these patients with advanced leukemia indicates that a trial of this regimen is warranted in children with less advanced ALL and ANLL.