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Biomedical subjects

C A Seipp

Publications and source records attributed to C A Seipp.

34 records · Page 2Linked to original sources
PubMed1986

A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2.

A new approach to cancer therapy has been developed based on the adoptive transfer of autologous lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (IL-2). Forty-one patients with advanced cancer who have failed all standard treatments were treated in this experimental protocol. Fourteen patients experienced an objective regression of cancer, including one patient with metastatic melanoma who underwent a complete regression. Objective responses were seen in patients with colorectal cancer, renal cell cancer, melanoma, and lung adenocarcinoma. The sites of tumor regression included subcutaneous tissue, lung, and liver. The major side effect of therapy resulted from the administration of high-dose IL-2 and was manifested primarily as fluid retention, resulting in a generalized capillary permeability leak syndrome. This approach to adoptive immunotherapy represents a promising approach to the therapy of patients with metastatic cancer. Attempts to increase the potency and decrease the toxicity of therapy and extend this treatment to patients with smaller tumor burdens are in progress.

Cell Separation↗
PubMed1985

Patterns of recurrence in patients with high-grade soft-tissue sarcomas.

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Perioperative blood transfusions are associated with increased rates of recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.

One hundred fifty-six patients with high-grade soft-tissue sarcomas of the extremities treated on prospective randomized trials were analyzed to determine the impact of perioperative blood transfusions on tumor recurrence and patient survival. A significant increase in the incidence of tumor recurrence and decrease in survival were associated with the receipt of blood transfusions at the time of definitive surgical therapy of the sarcoma. Actuarial 5-year continuous disease-free survival was 70% in patients who had not been transfused compared to 48% in patients who received one or more transfusions (P = .007). Overall 5-year survival was also substantially decreased in patients receiving transfusions (85% compared to 63%; P = .0035). A direct relationship existed between the number of transfusions administered and the decrease in disease-free and overall survival; the larger the number of transfusions the worse the prognosis (P less than .0001 and P = .0001, respectively). A large number of other prognostic factors were included in the analysis including the age, sex, race of the patient, histology of the primary lesion, anatomic site of the primary lesion, final surgical margins, size of the tumor, type of surgery required, the use of chemotherapy, actual time in the operating room under anesthesia, the exact anesthetic agent used, and the individual surgeon who performed the operation. Accounting for all of these factors a strong association continued to exist between the receipt of blood transfusion and poor patient prognosis. We have previously shown that adjuvant chemotherapy is of benefit to patients with high-grade extremity sarcomas, and 132 (84.6%) of 156 patients in this series received chemotherapy. In patients receiving chemotherapy, blood transfusions were associated with increased recurrence (P less than .0001) and decreased survival (P = .0001). The only other significant independent prognostic variable in these patients was the size of the primary tumor. An analysis of all patients, stratified for tumor size, revealed an impact of transfusions on increasing recurrence (P = .007) and decreasing survival (P = .016). An analysis of the subpopulation of patients with large tumors (greater than 150 mL) gave the same results (P = .03 and .015, respectively). It thus appears that the receipt of blood transfusions is associated with increased tumor recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1985

In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2.

Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies. Toxicity was dose related and included fever, chills, malaise, arthralgias, myalgias, and unexpectedly, weight gain related to marked fluid retention. All patients receiving more than 10(5) U/kg total cumulative dose developed evidence of fluid retention, and all patients requiring discontinuance of RIL 2 (11/20) received total doses of between 2.54 X 10(5) U/kg to 15.4 X 10(5) U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 10(6) U/kg by bolus administration. IL 2 was rapidly cleared from the plasma, with a half life of 6.9 min, and a later delayed clearance was consistent with a two-compartment model, with slower release from the extravascular space back into the plasma compartment. A marked change in lymphoid cells in the periphery was noted with an early depletion of all lymphoid cells, followed by an expansion of such cells with continuous IL 2 administration. A twofold to 16-fold expansion of total lymphoid cells in the peripheral blood could be demonstrated. TAC+ cells representing up to 25% of the circulating peripheral blood mononuclear cells could be demonstrated with 3 wk of continuous RIL 2 administration. Interferon-gamma levels increased in patients treated with IL 2. Precursors of lymphokine-activated killer cells generated under standard conditions were depleted within 2 to 3 min after IL 2 administration, but repopulated the peripheral blood after 7 to 10 days of continuous IL 2 administration. No tumor regression was seen in any of the cancer patients treated with IL 2 alone.

Adrenocorticotropic Hormone↗
PubMed1981

A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy.

A randomized, double-blind, placebo-controlled trial of oral and smoked delta-9-tetrahydrocannabinol (THC) was performed in eight patients with resected soft tissue sarcomas who received adjuvant Adriamycin and Cytoxan chemotherapy. Each patient served as his own control. Delta-9-tetrahydrocannabinol, in comparison with a placebo, did not significantly reduce the number of vomiting and retching episodes, volume of emesis, degree of nausea, or duration of nausea. In contrast to a previous report where significant antiemetic effects of THC were observed in patients receiving high-dose methotrexate, THC did not effectively reduce emesis induced by Adriamycin and Cytoxan. These findings suggest that the antiemetic properties of THC are effective only against specific chemotherapeutic drugs.

Adolescent↗
PubMed1979

Delata-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation.

Fifteen patients with osteogenic sarcoma receiving high-dose methotrexate chemotherapy were studied in a randomized, double-blind, placebo-controlled trial of oral and smoked delta-9-tetrahydrocannabinol (THC) as an antiemetic. Each patient served as his or her own control. Fourteen of 15 patients had a reduction in nausea and vomiting on THC as compared to placebo. Delta-9-tetrahydrocannabinol was significantly more effective than placebo in reducing the number of vomiting and retching episodes, degree of nausea, duration of nausea, and volume of emesis (P less than 0.001). There was a 72% incidence of nausea and vomiting on placebo. When plasma THC concentrations measured less than 5.0 ng/mL, 5.0 to 10.0 ng/mL, and greater than 10.0 ng/mL, the incidences of nausea and vomiting were 44%, 21%, and 6%, respectively. Delta-9-tetrahydrocannabinol appears to have significant antiemetic properties when compared with placebo in patients receiving high-dose methotrexate.

Adolescent↗
PubMed1979

Treatment of osteogenic sarcoma. II. Aggressive resection of pulmonary metastases.

Thirty-nine patients with osteogenic sarcoma were treated in a prospective protocol involving the use of adjuvant high-dose methotrexate, frequent screening for pulmonary metastases, and aggressive resection of all metastatic disease whenever possible. Twenty-two of these 39 patients have had recurrence and in 20 patients evidence of metastatic disease was confined to the lungs. Eighteen of the patients had thoracotomy, and in 11 patients all known disease was resected. Although four of these patients have required further thoracotomies, all 11 patients have no evidence of disease. Thus, of the original 39 patients, 30 (76.9%) are now alive and 28 (71.8%) have no evidence of disease, with a median followup of 27 months. Survival is significantly improved compared to historical control patients (P less than 0.001; one-sided Kruskal-Wallis test).

Antineoplastic Agents↗
PubMed1979

Treatment of osteogenic sarcoma. I. Effect of adjuvant high-dose methotrexate after amputation.

Thirty-nine patients with extremity osteogenic sarcoma and no discernible metastases were treated with amputation and postoperative adjuvant high-dose methotrexate with leucovorin rescue. One half of the patients were also randomized to receive bacillus Calmette-Guérin by a multiple-puncture technique. Results have been analyzed with a minimum followup of 10 months and a median followup of 27 months. Actuarial analysis estimates that 38% of current protocol patients remain continuously free of disease for 24 months compared to only 17.4% of historical control patients (P = 0.029; one-sided generalized Kruskal-Wallis test). Bacillus Calmette-Guérin administered by a multiple-puncture technique had no effect on disease-free interval. Minor differences between current protocol and historical control patients with regard to race, age, histologic type, and site and size of primary tumors do not affect the difference in disease-free interval between these two patient groups. However, current patients had somewhat lower grade lesions and consideration of the patients with grade III and IV lesions only, lessens the difference between current and historical control patients (P = 0.11; one-sided generalized Kruskal-Wallis test). High-dose methotrexate was administered with virtually no morbidity and no deaths. The small differences observed in this study between protocol patients treated with surgery plus high-dose methotrexate and historical control patients treated with surgery alone point to the need for a prospective randomized study to establish the role of high-dose methotrexate in the adjuvant treatment of patients with osteogenic sarcoma.

Adolescent↗
PubMedDate not supplied

A prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of nystatin on the development of oral irritation in patients receiving high-dose intravenous interleukin-2.

Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects. One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin. The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2. No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects. Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients.

Adult↗
PubMedDate not supplied

Effects of high-dose methotrexate and vincristine on ovarian and testicular functions in patients undergoing postoperative adjuvant treatment of osteosarcoma.

We have studied gonadal function in five patients (three men and two women) who received high-dose methotrexate (HD-MTX) alone and in 12 patients (seven men and five women) who received HD-MTX and vincristine (VCR) as postoperative adjuvant therapy for osteosarcoma. Testicular function was assessed by determination of testicular size, sperm concentration, and serum follicle-stimulation hormone (FSH), luteinizing hormone (LH), and testosterone levels while evaluation of ovarian function was based on menstrual history and serum FSH, LH, estradiol, and progesterone levels. The two women who received HD-MTX and all five women who received HD-MTX and VCR had regular cyclic menses not only after therapy but also during treatment. Serum FSH, LH, estradiol, and progesterone levels were normal in all women studied. Among the ten men studied, testicular function was normal in the six patients evaluated initially several months after the completion of therapy. In contrast, severe oligospermia was noted among four men evaluated during and immediately after treatment. From serum samples obtained before, during, and after treatment we have determined that approximately one half of the men who received HD-MTX alone or in combination with VCR develop transient testicular failure associated with a significant increase in serum FSH but not LH levels. Sperm concentration and serum FSH levels then return to normal after completion of chemotherapy.

Adolescent↗
PubMedDate not supplied

Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2.

OBJECTIVE: To determine the efficacy of treatment using high-dose bolus interleukin 2 (IL-2) in patients with metastatic melanoma or renal cell cancer. DESIGN AND SETTING: Consecutive series of all patients treated with high-dose IL-2 in the Surgery Branch of the National Cancer Institute from September 1985 through December 1992. PATIENTS: Two hundred eighty-three patients with metastatic melanoma or metastatic renal cell cancer who had failed standard treatment for their cancers. INTERVENTIONS: Patients received IL-2 at a dose of 720,000 IU/kg intravenously every 8 hours for a maximum of 15 doses per cycle. Two cycles constituted a treatment course, and patients with stable or responding disease received additional treatment courses. A total of 447 courses of treatment were administered. MAIN OUTCOME MEASURES: Regression of measurable tumor, durability of response to treatment, and survival. RESULTS: Nine patients (7%) with metastatic melanoma achieved complete regression of all disease and 14 patients (10%) had partial regression. Ten patients (7%) with metastatic renal cell cancer experienced complete regression and 20 patients (13%) had partial regression. Of the 19 patients with complete regression, 15 have remained in complete remission from 7 to 91 months after treatment. Three treatment-related deaths (1.1%) occurred early in this series, but as experience with the administration of this IL-2 regimen increased, no treatment-related deaths occurred in 214 patients treated during the last 5 years of the study. CONCLUSION: Biologic therapy with IL-2 can cause significant antitumor effects in patients with advanced metastatic melanoma or renal cell cancer. Because IL-2 does not have a direct effect on cancer cells but rather mediates its antitumor activity by altering host immune reactions, these data represent the best available evidence that immunologic therapy for cancer can be effective in selected patients.

Adolescent↗