Biomedical subjects

D E White

Publications and source records attributed to D E White.

At least 37 records · Page 2Linked to original sources

PubMed1995

HLA associations in the antitumor response against malignant melanoma.

In this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAC) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: of these, HLA-B5, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response. There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2.

Gene Frequency↗

PubMed1995

Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone.

The purpose of this prospective study was to determine the incidence of thyroid dysfunction in cancer patients receiving immunotherapy with interleukin-2 (IL-2) alone, and to assess the relationship of hypothyroidism to clinical response. A cohort of 281 consecutive patients with metastatic melanoma or renal carcinoma were treated with IL-2 alone from July 1, 1989 until June 30, 1993. The majority (n = 216) received high-dose IL-2 and the remainder (n = 65) received low-dose therapy. Thyroid function was measured before, during, and after immunotherapy. Forty-one percent of initially euthyroid patients developed thyroid dysfunction after starting high-dose IL-2-alone therapy. The most common abnormality was hypothyroidism, occurring in 35% of patients, although moderate or severe hypothyroidism requiring thyroid hormone replacement occurred in 9% of patients. Hypothyroidism was related to duration of IL-2 therapy and was not associated with clinical response. Hyperthyroidism developed in 7% of previously euthyroid patients receiving high-dose IL-2. Overall, the incidence of thyroid dysfunction was similar in the high- and low-dose IL-2 regimens. In conclusion, thyroid dysfunction is a common sequela of IL-2 therapy. Thyroid function should be measured routinely in cancer patients receiving IL-2-based treatment. It is recommended that thyroid hormone replacement be given to patients with moderate or severe hypothyroidism.

Adolescent↗

PubMed1995

Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer.

PURPOSE: Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFN alpha) and interleukin-2 (IL-2) in patients with metastatic cancer. PATIENTS AND METHODS: From November 1987 through October 1990, 189 patients were treated with 379 courses. IFN alpha (3 x 10(6) U/m2) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m2 (six patients, group 1), 7.8 x 10(6) IU/m2 (32 patients, group 2), or 11.7 x 10(6) IU/m2 (26 patients, group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m2 plus IL-2 11.7 x 10(6) IU/m2 (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10(6) IU/m2 (29 patients, group 5) and 15.6 x 10(6) IU/m2 (74 patients, group 6); however, because of IFN alpha-related toxicity, these two groups received IFN alpha once per day (6 x 10(6) U/m2). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval. RESULTS: All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFN alpha three times per day), no benefit for survival and increased toxicity were noted in this group. CONCLUSION: Based on these findings, we conclude that further studies of this combination treatment are not warranted.

Adolescent↗

PubMed1994

Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma.

BACKGROUND: Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed. METHODS: The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity. RESULTS: One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037). CONCLUSIONS: Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible.

Adolescent↗

PubMed1994

Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2.

BACKGROUND: Studies of human tumor-infiltrating lymphocytes (TILs) derived from patients with a variety of histologic types of cancer have demonstrated that cellular immune reactions against established malignancy exist in humans. PURPOSE: We report the results of using autologous TILs plus high-dose bolus interleukin 2 (IL-2), with or without the concomitant administration of cyclophosphamide, in the treatment of 86 consecutive patients with metastatic melanoma. METHODS: From May 1987 through December 1992, 86 patients (38 female and 48 male) with metastatic melanoma were treated (145 courses) with autologous TILs plus high-dose intravenous bolus IL-2 (720,000 IU/kg every 8 hours). TILs plus IL-2 were administered in two cycles separated by approximately 2 weeks. Two treatment cycles constituted one treatment course. Patients received a maximum of 15 doses of IL-2 per cycle given every 8 hours until grade 3 or 4 toxicity was reached that could not easily be reversed by standard supportive measures. All patients received concomitant medications to abrogate some of the side effects of IL-2 administration: acetaminophen (650 mg every 4 hours), indomethacin (50 mg every 8 hours), and ranitidine (150 mg every 12 hours). Fifty-seven of the 86 patients received a single intravenous dose of 25 mg/kg cyclophosphamide approximately 36 hours before receiving the first intravenous infusion of TILs plus IL-2. Six weeks after treatment, all known sites of disease were evaluated. RESULTS: The overall objective response rate in these patients was 34% and was similar in patients receiving TILs and IL-2 alone (31%) or in conjunction with cyclophosphamide (35%). There was no significant difference in the objective response rate in patients whose therapy with high-dose IL-2 had failed (32%) compared with patients not previously treated with IL-2 (34%). The frequency of response to treatment was greater in those patients who were treated with TILs from younger cultures (P = .0001), TILs with shorter doubling times (P = .03), and TILs that exhibited higher lysis against autologous tumor targets (P = .0008). Patients who received TILs generated from subcutaneous tumor deposits had higher response rates (49%) compared with those receiving TILs from lymph nodes (17%; P = .006). There was one treatment-related death due to respiratory insufficiency. CONCLUSIONS: Treatment with TILs and IL-2 with or without cyclophosphamide can result in objective responses in about one third of patients with metastatic melanoma. The side effects of treatment are transient in most patients, and this treatment can be safely administered. These results illustrate the potential value of immune lymphocytes for the treatment of patients with melanoma.

Adolescent↗

PubMed1994

A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy.

Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal carcinoma.

PURPOSE: To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. PATIENTS AND METHODS: One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. RESULTS: Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. CONCLUSION: High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified.

Adolescent↗

PubMed1994

In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2.

PURPOSE: To correlate in vitro characteristics of tumor-infiltrating lymphocytes (TIL) with clinical response to TIL immunotherapy in patients with metastatic melanoma. PATIENTS AND METHODS: Forty-one melanoma patients undergoing 43 separate treatment courses with TIL and interleukin-2 (IL-2) from December 1990 through November 1992 were studied prospectively. Multiple patient and treatment characteristics were evaluated for response correlates. In addition, TIL were assayed within 7 days of infusion for characteristics such as doubling time, cell-surface phenotype, autologous tumor lysis in 4-hour chromium-51 release assays, and cytokine secretion following autologous tumor stimulation. RESULTS: Nine patients experienced complete or partial tumor regressions. Clinical parameters such as age, sex, sites of disease, performance status, and prior therapies were similar in responders and nonresponders. Treatment variables such as the cumulative IL-2 dose and concomitant administration of cyclophosphamide or interferon (IFN)-alpha were not predictive of response, although responders received 33% more TIL. However, statistically significant differences in favor of clinical response were noted for extranodal source of TIL (v lymph node), shorter culture duration (mean, 38 v 47 days), shorter TIL doubling time (2.6 v 3.7 days), greater autologous tumor lysis by TIL (30% v 15%; effector-to-target [E:T], 40:1), and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by TIL following autologous tumor stimulation (six of nine responders v eight of 32 nonresponders). CONCLUSION: The associations of TIL lysis of autologous tumor and younger TIL age with clinical response observed in this study are supportive of previous reports, and these findings will be useful in designing future clinical trials. The new observation correlating GM-CSF secretion by TIL with clinical response is interesting and needs further substantiation.

Adult↗

PubMed1994

Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.

PURPOSE: A randomized prospective study was performed to compare the efficacy and toxicity of high-dose intravenous bolus interleukin-2 (IL-2) and a lower-dose intravenous bolus regimen for the treatment of metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between March 1991 and April 1993, 125 patients with metastatic RCC were randomized to receive IL-2 by intravenous bolus every 8 hours at either 720,000 IU/kg (high-dose) or 72,000 IU/kg (low-dose) to the maximum-tolerated number of doses (or a maximum of 15 doses). After approximately 7 to 10 days, both treatment groups were re-treated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5 to 6 weeks later went on to receive re-treatment with another course (two cycles) of therapy. Response rates and toxicity were determined for the two treatment arms. RESULTS: One hundred twenty-five patients received a total of 208 courses of therapy. Sixty patients were randomized to receive low-dose, and 65 to receive high-dose IL-2. There were no treatment-related deaths in either arm. There was a greater incidence of grade III or IV thrombocytopenia, malaise, and hypotension in patients who received high-dose IL-2, while patients who received low-dose IL-2 had significantly more infections. Three percent of treatment courses with low-dose IL-2 required vasopressor support, compared with 52% of courses with high-dose IL-2. Patients who received low-dose IL-2 had a 7% complete response (CR) and an 8% partial response (PR) rate, and patients who received high-dose IL-2 had a 3% CR and a 17% PR rate. CONCLUSION: Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU).

Adult↗

PubMed1993

High-grade retroperitoneal sarcomas: role of an aggressive palliative approach.

Between 1968 and 1988 we treated 41 patients with high-grade soft tissue retroperitoneal sarcomas. Clinical, pathological, and treatment variables were analyzed retrospectively with regard to their influence on recurrence rate and mortality. The actuarial 5-year median survival for the whole group was 48 months, with 33% of the patients surviving 10 years. Gender, clinical presentation, tumor size, and histological types did not predict outcome by multivariate analysis. Complete tumor resection was performed in 56% of the patients, but at 10 years after surgery only 10% of those patients remained disease free. Patients were classified into four groups according to the most aggressive surgical procedure employed: (1) total gross tumor resection; (2) subtotal resection, in which the major tumor bulk was excised (often with adjacent organs), but in which obvious residual disease remained; (3) palliative resection, in which minimal tumor resection was performed in order to alleviate symptoms; and (4) exploration only. Patients who were either explored and had no tumor removed or who underwent a palliative resection had a similarly poor prognosis, with a median survival of 12 and 20 months, respectively. To our surprise, patients after total resection had no survival benefit over patients who had undergone subtotal resection. However, both groups together had a significantly longer median survival of 241 months compared to the median survival of the patients with either no resection or only palliative resection (P < 0.02). The addition of chemotherapy or radiation therapy failed to show any advantage in this series. We claim from our experience that the impossibility of performing a complete resection should not prevent attempts at aggressive subtotal tumor excision, including the removal of adjacent organs, since this aggressive surgical approach may prolong survival significantly.

Combined Modality Therapy↗

PubMed1993

Combination chemoimmunotherapy for metastatic colorectal cancer using 5-fluorouracil, leucovorin and interleukin-2.

25 patients with metastatic colorectal cancer were entered into a phase II trial of combination chemoimmunotherapy using a sequential regimen of 5-fluorouracil (5-FU) and leucovorin and high-dose recombinant human interleukin-2 (rIL-2). Patients initially received three cycles of chemotherapy consisting of 500 mg/m2 of intravenous leucovorin followed by 375 mg/m2 of bolus 5-FU both given daily on days 1-5 of a 21 day cycle. Ten days after the last dose of chemotherapy in cycle 3, patients began high-dose rIL-2 at 720,000 IU/kg intravenously every 8 h to the maximum tolerated number of doses. After 7-10 days of recovery, this rIL-2 treatment was repeated to complete one full course of chemoimmunotherapy. There was no grade IV toxicity associated with 183 cycles of chemotherapy. Other than slight increases in the frequency of diarrhoea, stomatitis and hyperbilirubinaemia, rIL-2 toxicity was similar to that seen in patients given rIL-2 without chemotherapy. Of 23 evaluable patients, the overall response rate (partial + complete response) was 46% with 2 complete responses. Only 3 patients showed major tumour regression during the rIL-2 phase of therapy, but these 3 patients included both complete responders and the 3 most durable responses (15, 16 and 24 months). We conclude that sequential 5-FU/leucovorin and rIL-2 can be given safely without major increases in toxicity over either therapy alone, and although nearly all responses seen are largely attributable to chemotherapy, a contribution of immunotherapy to the minority of patients achieving complete or durable responses cannot be ruled out.

Adult↗

PubMed1993

Infectious complications associated with interleukin-2 administration: a retrospective review of 935 treatment courses.

PURPOSE: To determine if interleukin-2 (IL-2)-treated patients are prone to develop clinically significant infections, a retrospective review of 519 patients who received 935 treatment courses over a 38-month period was conducted. MATERIALS AND METHODS: Treatment records of patients receiving intravenous (IV) bolus IL-2 were reviewed. Clinically significant infectious episodes were identified by retrieving data on antibiotic usage and cross-referencing this with microbiology records and chart review. RESULTS: One hundred thirty-nine documented infectious episodes occurred in 122 treatment courses (13.0%); 11 courses were associated with more than one episode of infection. Predominantly urinary tract infections (6.8%) and infections related to IV catheters (5.3%) were encountered. Fifty-eight percent of the catheter-related infections were associated with bacteremia. Other infections included respiratory tract infections (1.0%), skin/muscle infections (0.9%), and miscellaneous infections (0.9%). Bacteria were isolated from the majority of infections. Almost all patients were successfully treated for their infection, with only two septic deaths (0.2%). No difference was noted in infected versus non-infected patients with regard to diagnosis or previous therapy. There was a significant tendency for those patients who developed infection to be older (P2 = .002, Mantel test for trend). Risk factors for the development of infection included vascular access catheters, open wounds, biliary obstruction, or incomplete treatment of previous infections. Over the 3-year study period, the incidence of infection declined from 23% to 7% (P2 < .0001, Mantel test for trend) due to rigorous patient screening, vigilant monitoring for infection, liberal use of antibiotics for suspected infection, and use of prophylactic antibiotics for central venous catheter placement. CONCLUSION: Although treatment with IL-2 may be associated with a slightly increased incidence of bacterial infections, these infections can be successfully managed in the great majority of cases.

Adolescent↗

PubMed1992

The use of interleukin-2 and lymphokine-activated killer cells for the treatment of patients with non-Hodgkin's lymphoma.

PURPOSE: The study was undertaken to assess whether immunotherapy regimens with bolus high-dose interleukin-2 (IL-2) alone or with lymphokine-activated killer (LAK) cells are active in previously treated, relapsed patients with non-Hodgkin's lymphoma. PATIENTS AND METHODS: Nineteen patients with low- or intermediate-grade lymphomas were treated with bolus high-dose IL-2 alone (11 patients) or IL-2 with LAK cells (eight patients). IL-2 was administered by intravenous bolus infusion at 720,000 IU/kg every 8 hours. Eight patients had low-grade histologies; 11 patients were intermediate-grade. Eighteen patients had received second- or third-generation combination chemotherapy, and eight had also received radiation. All 19 relapsed after a median of two chemotherapy regimens. RESULTS: Four responses were observed, three partial and one complete, in patients with follicular histologies who received IL-2 with LAK cells. Response durations were 10, 16, 16, and 26 months, and three responders were re-treated after relapse with subsequent disease control for an additional 16, 39+, and 2+ months, respectively. CONCLUSION: High-dose, bolus IL-2-based immunotherapy with LAK cells may be an effective treatment for patients with non-Hodgkin's lymphoma and merits further testing with larger numbers of patients in phase II trials.

Adult↗

PubMed1992

Intravenous administration of recombinant human macrophage colony-stimulating factor to patients with metastatic cancer: a phase I study.

PURPOSE: Recombinant human macrophage colony-stimulating factor (M-CSF) has been shown to stimulate specifically macrophage lineage differentiation in vitro and to induce cells capable of antitumor activity alone or in combination with an antibody. The administration of M-CSF to mice has demonstrated antitumor therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration to patients with metastatic cancer was undertaken. PATIENTS AND METHODS: M-CSF was given by intermittent intravenous bolus infusion every 8 hours for 7 days; the treatment cycle was repeated once after a week of rest. Cohorts of three patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23 patients received 27 courses of M-CSF administration. All patients had metastatic solid tumors refractory to conventional therapy, including renal cell carcinoma (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). RESULTS: Treatment-related toxicity was minimal; five patients developed transient signs of ocular or periorbital inflammation, with iridocyclitis as the most severe manifestation. At the highest doses, platelet counts decreased with therapy (but remained > 100,000/mm3) and the absolute monocyte count increased during the course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment limited because of toxicity (iritis and malaise). Pharmacokinetic studies demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal adenopathy and multiple pulmonary metastases were observed in one patient with RCC. CONCLUSION: Recombinant M-CSF can be administered safely to patients with metastatic cancer at doses that demonstrate biologic activity.

Adult↗

PubMed1992

A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas.

BACKGROUND: Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. METHODS: Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. RESULTS: Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. CONCLUSIONS: Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.

Adult↗

PubMed1991

Thyroid dysfunction associated with immunotherapy for patients with cancer.

The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin-2 (IL-2)-based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy-induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL-2-based immunotherapy.

Adolescent↗

PubMed1991

Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma.

A retrospective review is presented on 145 patients who underwent limb-sparing surgery and radiation therapy (with or without adjuvant chemotherapy) for their primary soft tissue sarcomas of the extremities on protocol between 1975 and 1986. The focus on our analysis was the acute and long term toxicity of treatment on limb function. The most common acute complication was skin reaction, occurring in 52 patients (36%). Long term (occurring after more than 1 year following all treatment) treatment complications in the extremity were as follows: bone fracture = 6%; contracture = 20%; pain requiring narcotics = 7%; edema greater than 2+ = 19%; moderate to severe decrease in range of motion = 32%; moderate to severe decrease in manual muscle strength = 20%; orthotic device required = 9%; cane or crutch required = 7%; chronic infection = 9%; and tissue induration = 57%. Three amputations for treatment complications were required. Inclusion of more than 50% of the joint in the radiation portal was associated with a higher frequency of contracture. High nominal standard dose (greater than 1760 rets, greater than 63 Gy at 1.8 Gy per fraction) resulted in more painful limbs as well as limbs with increased edema, decreased manual muscle strength, decreased range of motion, and skin telangiectasias. Edema was more often noted in patients with a longer radiation portal (greater than 35 cm), as was tissue induration. Chronic ulcer or infection was more frequently seen in patients with lower extremity tumors and when more than 75% of the extremity diameter was irradiated. Although chemotherapy given concurrent with radiation therapy was associated with a higher number of acute skin reactions, this did not appear to translate into increased long term morbidity. The percentage of patients ambulating without assistive devices and with mild or no pain was 84%. Careful attention to the techniques of radiation therapy may have a significant impact on minimizing acute and long term complications of limb sparing treatment for extremity soft tissue sarcoma.

Combined Modality Therapy↗

PubMed1989

Determinants of survival in patients with unresectable colorectal liver metastases.

Prognostic indicators in 67 patients with unresectable colorectal liver metastases were analyzed. These patients were identified to have isolated hepatic metastases after extensive radiological evaluation and demonstrated good performance status without evidence of liver failure. Univariate analysis revealed 6 of 22 factors that were associated with survival: alkaline phosphatase (AP), lactic dehydrogenase (LDH), occult intra-abdominal extrahepatic disease, percent hepatic replacement by tumor (PHR), sex, and carcinoembryonic antigen (CEA). A multivariate analysis identified two independent factors that jointly influenced survival: AP and PHR. Patients with an AP greater than 175 U/liter had a greater than threefold relative risk of dying compared with patients with AP less than or equal to 175 U/liter (P = 0.0001). Patients with PHR II or III (25-75%, greater than 75%) also had a greater than threefold relative risk of dying compared with patients with PHR 1 (less than 25%; P = 0.0074). Our patient population is typical of that being entered into trials examining experimental therapies. Alkaline phosphatase and extent of liver involvement by tumor are significant prognostic indicators that should be accounted for in such studies.

Aged↗