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Biomedical subjects

S Groshen

Publications and source records attributed to S Groshen.

At least 145 records · Page 8Linked to original sources
PubMed1987

Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial.

Combinations of metoclopramide and dexamethasone given intravenously control vomiting caused by high doses of cisplatin. Lorazepam and diphenhydramine are useful adjuncts to antiemetics. In a double-blind trial, 120 patients receiving high-dose cisplatin (120 mg/m2) for the first time were randomly assigned to receive either lorazepam (1.5 mg/m2) or diphenhydramine (50 mg) intravenously, 45 minutes prior to cisplatin. In addition, all patients received intravenous dexamethasone (20 mg) 40 minutes prior to chemotherapy along with metoclopramide (3 mg/kg) 30 minutes before and 90 minutes after cisplatin. Patients were directly observed in the hospital after cisplatin administration and completed a subjective assessment questionnaire. Overall, 60% of patients experienced no vomiting, and 83% had two or fewer emetic episodes during the study. There were no significant differences in objective antiemetic control between the two regimens. Only 3% of patients receiving lorazepam experienced treatment-related restlessness as opposed to 19% given diphenhydramine (P = 0.007). Less recall of chemotherapy administration (P less than 0.001), more sedation (P = 0.003), and transient enuresis while sedated (P = 0.0002) were characteristic of patients receiving lorazepam. Patient-generated ratings revealed less anxiety (P = 0.0001) for those individuals given the lorazepam-containing combination. Both regimens were well accepted, with 89% of patients receiving the lorazepam combination and 83% of those given the diphenhydramine regimen wishing to receive the same drugs in the future. Some degree of delayed vomiting occurred in 85% of patients during the 4-day period following this study. During the time that patients are at the greatest risk for emesis, the 24 hours immediately following cisplatin, three drug antiemetic combinations of either lorazepam or diphenhydramine with metoclopramide plus dexamethasone stopped cisplatin-induced emesis for the majority of patients and lessen other treatment-related side effects. Less restlessness and anxiety were observed among individuals receiving the lorazepam-containing combination.

Adult↗
PubMed1987

Association of serum iron, serum transferrin saturation, and serum ferritin with survival in acute lymphocytic leukemia.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.

Child↗
PubMed1986

2'-Fluoro-5-iodoarabinosylcytosine, a new potent antiviral agent: efficacy in immunosuppressed individuals with herpes zoster.

2'-Fluoro-5-iodoarabinosylcytosine (FIAC) has potent antiviral activity in vivo against herpes simplex virus types 1 and 2 and cytomegalovirus. For examination of the clinical efficacy of FIAC, a randomized, double-blind study of FIAC versus adenine arabinoside (ara-A) was conducted in 34 immunosuppressed individuals with varicella-zoster virus infections. The median time to the appearance of the last new lesion was shorter in patients who received FIAC relative to those who received ara-A (two versus five days, respectively; P less than .001) FIAC also reduced pain and accelerated initial crusting within 72 hr in a significantly greater proportion of patients when compared with ara-A (P = .004 and P = .0009, respectively). FIAC caused few toxic reactions (mild nausea and transient elevation in activity of serum aspartate aminotransferase). Thus FIAC is therapeutically superior to ara-A for the treatment of varicella-zoster virus infections in immunosuppressed subjects.

Adolescent↗
PubMed1986

Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy.

To determine the frequency and prognostic importance of pretreatment clinical characteristics in patients currently undergoing treatment for stage III non-small-cell lung cancer (NSCLC), data were collected on 378 patients receiving high-dose (120 mg/m2) cisplatin plus vinca alkaloid combination chemotherapy regimens since 1978. Variables analyzed included age, sex, weight loss, performance status, histologic subtype, presence of extrathoracic metastases, number of metastatic organ sites, presence of liver, bone, or brain involvement, prior radiation or surgery, and serum lactate dehydrogenase (LDH). The effect of a major response to chemotherapy on survival was also investigated. Using multivariable analyses, the following were found to be associated with outcome: initial performance status, with patients having a performance status of 80% to 100% having an increased major objective response rate and survival; bone metastases, which were adversely predictive of response rate and survival; elevated serum LDH and male sex, both of which were associated with shortened survival and remission duration; and the presence of two or more extrathoracic metastatic organ sites, which was associated with shorter survival. When major objective response with chemotherapy was included in a conditional multivariable analysis, it was strongly associated with longer median survival. Information from this analysis may be useful when comparing the response data of completed studies in similar patients, in designing future trials, and in the selection of cisplatin plus vinca alkaloid therapy for individual patients with advanced NSCLC.

Adult↗
PubMed1985

Survival in bilateral breast cancer.

The presence of bilateral invasive breast cancer places the patient in a state of double jeopardy. At Memorial Sloan-Kettering Cancer Center, the overall 10-year recurrence rate for unilateral Stage I breast cancer was 16%, whereas the recurrence rate for simultaneous, bilateral Stage I breast carcinoma was 29%: almost twice as high. The average 10-year survival of all patients with negative axillary nodes was 57%. In this retrospective analysis of 403 patients with bilateral primary operable breast cancer treated at Memorial Sloan-Kettering Cancer Center, significant differences were noted in the disease-free survival between patients with bilateral noninvasive cancer, bilateral invasive cancer, and the combination of invasive and in situ cancers. Bilateral intraductal cancer and lobular carcinoma in situ offered an excellent prognosis. The combination of preinvasive cancer on one side and infiltrating carcinoma on the other had the next best survival. The in situ lesion, when treated by mastectomy, did not alter the patients' life expectancy from that of the general population with unilateral breast cancer, thus indicating that surgeons should strive to detect breast cancer in its preinvasive form. The 5- and 10-year relapse-free survival of patients with bilateral invasive disease, regardless of axillary nodal status and tumor size, was 60% and 51%, respectively, for patients with a bilateral presentation and 54% and 38%, respectively, for carcinomas presenting metachronously. More important in determining prognosis, however, was the number of axillary nodes involved and the level of involvement. Invasion of bilateral axillary nodes at all levels predicted a poor prognosis. Because of this shortened survival, systemic adjuvant therapy should be considered for patients with bilateral invasive disease. The most common preinvasive breast cancer was lobular carcinoma in situ and the most frequently invasive tumor was infiltrating duct cancer. Since a contralateral breast cancer at the time of definitive treatment of the first side does not always present as a mass or with positive mammography, a random biopsy of the second breast is recommended. This should be done in the upper, outer quadrant and should include the subareolar area. With prompt adequate treatment, it is expected that survival from bilateral breast cancer should improve.

Breast Neoplasms↗
PubMed1985

Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients.

A series of consecutive trials were undertaken to determine whether higher doses of intravenous metoclopramide and combinations of metoclopramide, dexamethasone, and diphenhydramine would improve antiemetic control or decrease treatment-related side effects in patients receiving cisplatin at 120 mg/m2. Metoclopramide and dexamethasone were studied because of their proven efficacy as single agents and their differing mechanisms of action and side effects. Diphenhydramine was used because of its possible antiemetic properties and its ability to control acute dystonic reactions. Two hundred fifty-five patients who had never received chemotherapy or antiemetics were observed in the hospital for the 24 hours following cisplatin administration. The addition of dexamethasone or dexamethasone plus diphenhydramine to intravenous metoclopramide 2 mg/kg produced both improved antiemetic control and a decrease in treatment-associated diarrhea (P = 0.002). The use of metoclopramide alone at a dose of 3 mg/kg for only two doses appeared as effective as 2 mg/kg for five doses. When dexamethasone and diphenhydramine were given with metoclopramide 3 mg/kg for two intravenous dosages, 81% of patients experienced no emesis and 93% had two or fewer vomiting episodes. The antiemetic results of this 2-hour "short-course" regimen were superior to metoclopramide 2 mg/kg, with (P = 0.002) or without (P = 0.0001) dexamethasone and diphenhydramine. It was concluded that combinations of metoclopramide plus dexamethasone plus diphenhydramine improve antiemetic control, facilitate the usage of higher doses of metoclopramide, and decrease the incidence of treatment-related side effects.

Adult↗
PubMed1985

ABH blood group isoantigen expression in breast carcinomas--an immunohistochemical evaluation using monoclonal antibodies.

The ABH blood group isoantigen status of a retrospective series of 233 invasive breast carcinomas was examined, employing monoclonal antibodies (MCAB) against A, B, and H antigens with the avidin-biotin-peroxidase complex method. In addition, the H antigen was localized with Ulex Europeus Agglutinin I (UEAI) binding. The MCABs provided consistent and specific staining of erythrocytes and endothelium, as well as normal and neoplastic breast epithelium. The anti-H MCAB yielded cleaner background and less intense staining, but otherwise the staining distribution was comparable to the UEA I technique. Contrary to previous reports, deletion of isoantigen expression was not universal in all invasive carcinomas. Whereas 64%, 77%, and 73% of carcinomas from groups A, B, and AB patients, respectively, demonstrated total isoantigen loss, the remaining tumors exhibited variable degrees of isoantigen expression. Moreover, those carcinomas with complete loss of A and B determinants still displayed variable degrees of H immunoreactivity. Carcinomas from group O patients had different degrees of H antigen deletion, with only 12% showing total loss. Statistical analysis revealed that the isoantigen status bore no significant relationship to various epidemiologic, clinical, and pathologic parameters and did not serve as a useful prognostic determinant.

ABO Blood-Group System↗
PubMed1985

Tumor marker expression in breast carcinomas and relationship to prognosis. An immunohistochemical study.

A collaborative immunohistochemical study was carried out to examine the expression and prognostic significance of tumor markers in a retrospective series of 233 invasive breast carcinomas. The patterns of tumor marker expression in 94 patients with short remission duration (recurrence within five years) were compared with 50 patients with intermediate (at five to ten years) and 89 patients with long (no recurrence at ten years or longer) remission durations. The antigens examined were carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), placental lactogen, alpha-lactalbumin, and pregnancy-specific beta-1 glycoprotein. Carcino-embryonic antigen was the most frequently expressed antigen, whereas HCG was demonstrated least frequently. Also, the ABH isoantigen status was examined using monoclonal antibodies; isoantigen expression was observed in a subset of breast carcinomas, contrary to previous reports of total deletion in breast cancer. Two of the markers, CEA and HCG, were examined by both laboratories, each with two different antisera and also with both PAP and ABC immunohistochemical technics. Meticulous efforts were taken to provide quality control and ensure reproducibility of results. These included the use of serial sections of duplicate pathologic material by both institutions, standardization of experimental conditions and interpretation criteria, double-blind evaluation of exchanged slides, and use of standardized data sheets to record staining extent and intensity. No significant disagreements were observed between data obtained through the different approaches. The steps that were taken to minimize interobserver and interinstitutional differences in this study are presented as a model for collaborative immunohistochemical studies. The expression of tumor markers, alone or in combination, was not found to bear any significant relationship to prognostic indicators, such as the likelihood of recurrence, interval before recurrence, or presence of metastasis.

ABO Blood-Group System↗
PubMed1985

Ferritin in neuroblastoma. Impact of tumor load and blood transfusions.

Serial serum ferritin (SF) levels were measured in 36 patients with neuroblastoma seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1981 and December 1982. The significance of the associations among SF, stage and extent of disease, number of blood transfusions, liver function, serum iron (Fe), total iron-binding capacity (TIBC), and transferrin saturation was investigated. Although a dominant statistical correlation was found between SF and number of blood transfusions, the results suggest that amount of disease contributes to increasing SF levels. Serum ferritin levels increased on average in a linear fashion with number of blood transfusions in patients free of disease or with minimal disease. In patients with bulky disease, this increase was exponential (p value less than 0.01). Application of a reverse hemolytic plaque assay to the analysis of ferritin secretion by cells demonstrates that tumor cells do secrete ferritin in vitro.

Adolescent↗
PubMed1985

Randomized trial comparing vindesine plus cisplatin with vinblastine plus cisplatin in patients with non-small cell lung cancer, with an analysis of methods of response assessment.

One hundred eight patients with stage III non-small cell lung cancer were randomly assigned to receive cisplatin (120 mg/m2) with either vindesine (3 mg/m2) or vinblastine (6 mg/m2). None had previously received chemotherapy. An additional goal was to determine if the observation of visible evaluable lesions was as accurate a method of response assessment as the observation of bidimensionally measurable lesions in non-small cell lung cancer. When vindesine plus cisplatin was compared to vinblastine plus cisplatin, response rates (33% vs 41%), median response durations (8.6 vs 5.6 months), and median survival times of responding patients (18.4 vs 16.2 months) were similar. Response rates, response durations, and survival times of responding patients determined through the observation of evaluable or measurable indicator lesions did not differ significantly. More patients receiving vinblastine plus cisplatin experienced wbc counts less than 2100/mm3 (P = 0.003). The two regimens demonstrated comparable response and survival data but clinically significant leukopenia was more common in vinblastine-treated patients. There was no difference in response data obtained through the study of patients with measurable and evaluable indicator lesions.

Adenocarcinoma↗
PubMed1985

Consecutive dose-finding trials adding lorazepam to the combination of metoclopramide plus dexamethasone: improved subjective effectiveness over the combination of diphenhydramine plus metoclopramide plus dexamethasone.

Four consecutive trials were undertaken to study lorazepam at each of three dosage levels and diphenhydramine when used in combination with iv metoclopramide and dexamethasone in patients receiving cisplatin at 120 mg/m2. The combination containing diphenhydramine had been the most effective treatment identified in prior trials. Earlier studies have found lorazepam to be a useful adjunct to other antiemetic agents. Sixty-five patients who had never received chemotherapy or antiemetics were directly observed in the hospital for 24 hours following cisplatin. Overall, 56% of the patients experienced no emesis and 78.5% of the patients had two or fewer vomiting episodes during the study period. No significant differences were noted in the number of patients who experienced no emesis or two or fewer episodes among the four trials. More sedation was seen with the lorazepam-containing regimens; other side effects were similar in type and severity. The trial using the highest dose of lorazepam (1.5 mg/m2) demonstrated significantly greater patient satisfaction (P = 0.039) and less anxiety during therapy (P = 0.02) when compared with the diphenhydramine combination. We conclude that combinations of iv metoclopramide plus dexamethasone with either diphenhydramine or lorazepam are well tolerated and effective in controlling cisplatin-induced emesis. The regimens containing lorazepam produced better subjective evaluations, and the combination using the highest lorazepam dose tested showed superior patient satisfaction and less anxiety during therapy.

Adult↗
PubMed1984

Nutritional rehabilitation in patients with advanced head and neck cancer receiving radiation therapy.

Previous studies of nutritional support in cancer patients have applied parenteral techniques for relatively short periods. The purpose of this prospective, randomized trial was to evaluate the efficacy of long-term enteral alimentation in patients at high risk for malnutrition during oncologic treatment. Forty patients with inoperable squamous carcinoma of the nasopharynx and oropharynx were randomized to either optimal oral nutrition or to intensive nasogastric tube feedings during radiation therapy for an average of 8 weeks. Dietetic counselling and oral supplements were provided to both groups. Body weight, dietary intake, and toxicity to therapy were assessed weekly; and serum protein concentrations and anthropometric measurements were made at the time of entry, during the fourth week, at the conclusion of radiation therapy, and 1 month after radiation therapy. Tumor status was assessed at the conclusion of radiation therapy and during routine follow-up, which ranged from 9 to 39 months. The 35 evaluable patients (18 tube fed and 17 orally fed) were comparable with regard to age, disease site, and total radiation dosage, but the tube group had more stage IV patients and a greater median radiation field size. The tube fed group showed no difference in the partial tumor response rate compared with the complete tumor response rate (16 of 18 patients versus 14 of 17 patients), a slightly longer duration of response in those who had recurrence compared with those without recurrence (4.5 months versus 3.4 months) and a similar overall survival pattern to that of the orally fed group. Compared with the orally fed group, the tube fed group had a higher mean caloric intake (39 kcal/kg per day versus 30 kcal/kg per day, p less than 0.001), mean protein intake (1.4 versus 1.1 g/kg per day, p less than 0.01), and in the oropharynx cancer patients, less mean body weight loss (0.6 percent versus 6.1 percent, p less than 0.04) during treatment. The tube fed patients maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.

Administration, Oral↗
PubMed1984

Primary osteogenic sarcoma of the femur: a model for the use of preoperative chemotherapy in high risk malignant tumors.

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Adolescent↗
PubMed1984

Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia.

Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.

Acute Disease↗
PubMed1983

Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy.

Since October 1973, 185 patients 21 years of age or younger with primary osteogenic sarcoma of an extremity were treated with adjuvant chemotherapy. Twenty-five of the first fifty-two patients (48%) have remained free of disease for a median of 7 years. In the next chemotherapy protocol most patients had chemotherapy prior to amputation or resection, during which time the dose of high-dose methotrexate was escalated in many patients to that needed to shrink the primary tumor. For a median of 4 years 43 of 54 patients (80%) have remained free of disease. In the current protocol, the response of the primary tumor to chemotherapy with high-dose methotrexate was used to select postoperative adjuvant chemotherapy for the patient. With the latter approach 73 of 79 patients (92%) have remained continuously free of disease for a median of 2 years. This experience demonstrates the value of chemotherapy in increasing the cure rate in osteogenic sarcoma and that the response to preoperative chemotherapy can help select postoperative chemotherapy to produce an even higher potential cure rate for osteogenic sarcoma.

Adolescent↗
PubMed1983

Ferritin secretion by human mononuclear cells: association with HLA phenotype.

A number of different observations indicate that cells of the immune system can participate in the prevention of potential tissue toxicity from iron accumulation and that, in turn, iron and iron binding proteins have important effects on immune responses. The current studies were undertaken to examine a specific aspect of the interaction of iron with human peripheral blood mononuclear cells. A modified hemolytic plaque-forming assay was used to measure ferritin secretion in vitro by phytohemagglutinin activated or nonactivated mononuclear cells in response to stimulation by ferric citrate. Cells from 55 unrelated healthy subjects collectively representing all well-defined HLA-A, B, C, and DR antigens were studied. There were large reproducible differences in the numbers of plaques formed by different individuals, and there was a statistically significant increase in the frequency of the HLA determinant A3 among the "low" responders. Ferritin secretion measured with an antibody specific for acidic ferritin also showed a distinction between A3 and non-A3 donors. In preliminary cell mixing studies, ferritin secretion by mononuclear cells was shown to require the presence of monocytes and to be influenced by the secretion characteristics of both the monocyte and the T-cell donor. These results may provide a clue to the mechanism of development of idiopathic hemochromatosis which is an HLA-A-linked autosomal recessive disease associated with the specific HLA antigen HLA-A3.

Cell Adhesion↗
PubMed1983

Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia.

Fifty-two patients with acute lymphoblastic leukemia (ALL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Twenty-two patients were in second remission, 15 in a later remission, and 15 were in relapse at the time of the transplant. At a median follow-up of 24 mo, 14 of those in second remission survive in continuous remission compared to 5 in later remission and 4 in the relapse group. Statistical analysis showed an improved disease-free survival for the second remission group (p = 0.09). Patients transplanted in later remission or relapse had a similar survival. The improved survival in second remission resulted from a decreased relapse rate posttransplant, as the early mortality from nonleukemic causes was similar among the groups (p = 0.01). In the second remission patients, no characteristics of the initial leukemia were identified that significantly affected outcome. In the combined later remission and relapse group, poor prognosis posttransplant was associated with initial WBC greater than 20K, age at diagnosis older than 10, or initial remission duration less than or equal to 1 yr. These results suggest that extended disease-free survival may be achieved by second remission transplantation and that improved therapy is necessary for later remission or relapse transplants due to the high rate of posttransplant relapse.

Adolescent↗