A Sella, B B Aggarwal, R G Kilbourn, C A Bui, A A Zukiwski, C J Logothetis
{"title":"Phase I study of tumor necrosis factor plus actinomycin D in patients with androgen-independent prostate cancer.","authors":"A Sella, B B Aggarwal, R G Kilbourn, C A Bui, A A Zukiwski, C J Logothetis","doi":"10.1089/cbr.1995.10.225","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.225","url":null,"abstract":"<p><p>Based on preclinical studies which reveal enhanced antitumor activity of tumor necrosis factor (TNF) when combined with actinomycin D in human prostate cancer cell lines, we performed a phase I clinical study combining TNF and actinomycin D. All patients had metastatic prostatic carcinoma exhibiting androgen-independent growth. Patients were treated with a combination of a short infusion of actinomycin D followed by a TNF infusion daily for five consecutive days. Soluble TNF receptor p60 was not modulated by treatment but p80 receptor increased significantly following treatment with a combination of TNF and actinomycin D (baseline median 3.4 ng/ml) range 2.5-6.6 ng/ml follow up (9.3 ng/ml) range 6-24 ng/ml. We concluded that the maximum tolerated dose of continuous infusion TNF and short infusion actinomycin D is 400 micrograms/m2 of actinomycin D and 400 micrograms/m2 of TNF. The increased soluble receptor isoform (p80) may account for the lack of clinical activity seen in this trial. Should these results be confirmed, a strategy focused on overcoming the upregulation of the TNF soluble receptor will be required before further study of TNF should be considered.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"225-35"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A Adler, J Schachter, Y Barenholz, L K Bar, T Klein, R Korytnaya, A Sulkes, R Michowiz, Y Cohen, I Kedar
{"title":"Allogeneic human liposomal melanoma vaccine with or without IL-2 in metastatic melanoma patients: clinical and immunobiological effects.","authors":"A Adler, J Schachter, Y Barenholz, L K Bar, T Klein, R Korytnaya, A Sulkes, R Michowiz, Y Cohen, I Kedar","doi":"10.1089/cbr.1995.10.293","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.293","url":null,"abstract":"<p><p>The aim of this pilot study was to assess the clinical and immunological effects of human allogeneic liposomal melanoma vaccine alone or combined with Interleukin-2 (IL-2) in patients with metastatic melanoma. Four concurrent treatment arms were included: vaccine alone (A); vaccine combined with systemic IL-2 (B); vaccine combined with low-dose liposomal regional IL-2 (C); and low-dose regional IL-2 as in group C but without vaccine (D). Vaccine was prepared from semisynthetic phospholipids (dimyristol phosphatidylcholine and dimyristol phosphatidylglycerol) and membranes of six human melanoma cell lines. The latter were chosen as expressing MHC class I and II antigens and a \"mosaic\" of melanoma-associated antigens (MAAs) as detected by MoAbs R24, p97, CF21 and TA99. Nine of the 24 patients had objective clinical responses: of the ten patients treated with liposomal vaccine and low dose regional IL-2 (arm C), three had complete responses (CR) and three had partial responses (PR); of the five patients treated with liposomal, low-dose regional liposomal IL-2 only (arm D), three had PRs. No clinical responses were seen in patients treated by vaccine alone (A) nor in patients treated by vaccine and systemic IL-2 (B). Patients' in vivo and in vitro cellular immune responses were closely monitored. Conversion to positive cutaneous delayed type hypersensitivity (DTH) to membrane vaccine (without liposomes) was induced only in the six clinical responders of arm C. Positive DTH correlated with augmented in vitro proliferative lymphocyte responses stimulated by melanoma cell lines and membrane preparation and with the augmented cytolytic activity against melanoma cell lines.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"293-306"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment of refractory low grade lymphoma with chlorambucil alternating with interferon and radiotherapy.","authors":"A Avilés, A Talavera, R Guzmán, I Cuadra","doi":"10.1089/cbr.1995.10.273","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.273","url":null,"abstract":"<p><p>We report the results of a clinical trial of chlorambucil (CB) alternating with interferon alfa 2b (IFN) in previously treated patients with low-grade lymphoma who were refractory to previous treatment. Patients received CB 10 mg/m2, po, daily, days 1-14, alternating with IFN 5.0 MU three times a week days 15-28 (six doses) by six monthly cycles. If partial response was achieved, patients received extended field radiotherapy to sites of nodal residual postchemotherapy disease. Forty-three patients were enrolled into the study, and 30 were evaluable for response and toxicity. Nineteen out of 39 (40%) achieved complete remission and 14 out of 39 (35%) had partial remission, thus the overall response was observed in 83% of the cases. Ten patients with partial response and residual nodal disease received radiotherapy and achieved complete response criteria. The median duration of response has not been achieved, yet, 23 patients remain in complete response after a median follow-up of 98.5 months. Toxicity was mild and 95% of the patients received the planned dose of CB and IFN. These results suggest that combination of CB and IFN and addition of radiotherapy to residual postchemotherapy nodal disease may be effective in patients with low-grade lymphoma without excessive toxicity and adequate quality of life.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"273-7"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Guida, I Abbate, A Casamassima, M D Musci, A Latorre, V Lorusso, M Correale, M De Lena
{"title":"Long-term subcutaneous recombinant interleukin-2 as maintenance therapy: biological effects and clinical implications.","authors":"M Guida, I Abbate, A Casamassima, M D Musci, A Latorre, V Lorusso, M Correale, M De Lena","doi":"10.1089/cbr.1995.10.195","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.195","url":null,"abstract":"<p><p>Several trials have evaluated the therapeutic efficacy of rIL-2 combined with more traditional treatments such as chemotherapy and radiotherapy, but the use of IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical response obtained with other standard treatments has yet to be investigated. The aim of the present trial was to study the biological effects of maintenance long-term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with different neoplasms previously treated with chemo-immuno therapeutic regimens or with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility and therapeutic implications are also discussed. The IL-2 schedule was as follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients completed therapy without requiring dose modifications and are free of progression after a median duration of 8+ months (range: 7+ to 34+) while two patients progressed during therapy (one inflammatory breast cancer and one renal cancer). Important and persistent hemato-immunostimulating effects in both soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes, eosinophils) parameters were noted during the entire treatment. The IL-2 related toxicity was quite low. Moreover, this long-term IL-2 therapy could control neoplastic growth and thus prolong clinical response obtained with standard treatments. Prospective randomized studies regarding the clinical efficacy have been initiated.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"195-203"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M E Marshall, M Wolf, E D Crawford, I M Thompson, R Flanigan, S P Balcerzak, F J Meyers
{"title":"Evaluation of low dose alpha-interferon (Roferon-A) in patients with advanced renal cell carcinoma: a Southwest Oncology Group study.","authors":"M E Marshall, M Wolf, E D Crawford, I M Thompson, R Flanigan, S P Balcerzak, F J Meyers","doi":"10.1089/cbr.1995.10.205","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.205","url":null,"abstract":"<p><p>Alpha-interferon (IFN) has been shown to produce antitumor responses among patients with advanced renal cell carcinoma. While responses have been observed over a range of IFN doses and schedules, significant toxicities can be experienced from relatively high doses given three to five times weekly. Based upon the report of a pilot study indicating that low dose daily IFN could produce antitumor responses with minimal toxicity, the Southwest Oncology Group investigated this schema in a phase II trial. Patients with bidimensionally measurable disease were treated with Roferon-A 1 million units subcutaneously daily and tumor assessments were conducted on a monthly basis. There were no dose escalations and no dose reductions for toxicity. The treatment was well tolerated with only two patients withdrawing from treatment because of side effects. Among 56 eligible patients treated, there were five partial responses and one complete response for an overall response rate of 11% (95% confidence interval, 4 - 22%). However, objective antitumor responses could not be determined for 16 of the 56 patients. Among the 40 fully evaluable patients the 6 objective responses yields a response rate of 15% (95% confidence interval, 5.7-30%). It is concluded that this dose and schedule of IFN has activity against advanced renal cell carcinoma. A randomized trial would be required to determine if this low dose regimen is as effective as the higher doses which have been used traditionally.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"205-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rhabdoid tumor of the kidney in an adult: review of the literature and report of a case responding to interleukin-2.","authors":"S W Ebbinghaus, G Herrera, M E Marshall","doi":"10.1089/cbr.1995.10.237","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.237","url":null,"abstract":"<p><p>Rhabdoid tumor of the kidney is an uncommon and highly aggressive malignancy usually found in the pediatric age group. This tumor does not respond well to aggressive chemotherapy regimens and survival tends to be short. Only two cases of rhabdoid tumor of the kidney occurring in adults have been described previously. The third case of a rhabdoid tumor of the kidney in an adult is presented here. This clinical case report is unique not only because of the rare occurrence of this tumor in adulthood but because the patient described had an objective antitumor response to outpatient low dose interleukin-2. This single case report may have therapeutic implications for other patients with this tumor.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 3","pages":"237-41"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner.","authors":"H J Nielsen, L J Petersen, P S Skov","doi":"10.1089/cbr.1995.10.279","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.279","url":null,"abstract":"<p><p>We previously observed that human, recombinant interleukin-2 in a pharmacologic dose (200 u/ml) induced histamine release from monocyte-depleted peripheral blood mononuclear cells in vitro. Therefore, we studied the role of various pharmacologic doses of rIL-2 on in vitro histamine release. Peripheral blood mononuclear cells (5 x 10(6) cells/ml), which also contain basophils, from 13 patients scheduled for elective colorectal cancer surgery and 10 age and sex matched healthy volunteers were stimulated with rIL-2 in concentrations of 0, 50, 100, 200, 450, 900, 1,800 and 3,600 u/ml, respectively, for 1, 24 and 48 hours under standard conditions. Histamine was analysed in supernatants using the glass fiber method. Simultaneously, total cell-bound histamine was analysed in lysate from 5 x 10(6) mononuclear cells from all patients and volunteers, thus allowing determination of percent histamine release. Supernatant histamine concentration from unstimulated cells was 17.2 +/- 1.5 ng/ml in patients compared to 7.9 +/- 1.0 ng/ml in volunteers (#p < 0.05) after 1 hour stimulation, and no further increase was observed after 24 and 48 hours, respectively. Histamine concentration increased significantly in the supernatant from cells stimulated by rIL-2 in a dose-dependent manner both in patients and volunteers. Total cell-bound histamine was 49.3 +/- 4.1 ng/ml in patients compared to 78.5 +/- 7.7 ng/ml in volunteers (p < 0.05). Therefore, both spontaneous and rIL-2-induced histamine release was significantly enhanced in cancer patients compared to volunteers (*p < 0.05). These data suggest that rIL-2 in high pharmacologic doses stimulates in vitro histamine release in a dose-dependent manner in both cancer patients and volunteers. This may in part explain the severe toxicity observed during high-dose rIL-2 therapy.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"279-86"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Whole body hyperthermia as a potential therapeutic option.","authors":"L M Shecterle, J A St Cyr","doi":"10.1089/cbr.1995.10.253","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.253","url":null,"abstract":"","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 4","pages":"253-6"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19570524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Kariya, K Nakamura, K Nomoto, Y Kobayashi, M Namiki
{"title":"Superoxide dismutase (SOD) activity with Fe-chlorin e6-Na and suppression of malignant tumor growth in rats.","authors":"K Kariya, K Nakamura, K Nomoto, Y Kobayashi, M Namiki","doi":"10.1089/cbr.1995.10.139","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.139","url":null,"abstract":"<p><p>Derivatives of porphyrin, specifically Fe-chlorin e6-Na (FeCNa), mimic superoxide dismutase (SOD). This SOD activity was determined by decrease in electron spin resonance (ESR) signals and increase in hydrogen peroxide (H2O2) as the intermediate of O2-. by the coloration using 4-aminoantipyrin. Chlorin e6-Na used for cancer photodynamic therapy (PDT)(1) does not show SOD mimicking activity. The specific activity of FeCNa, comparing with bovine RBC-SOD, was 1/7.5 as determined by ESR analysis. The iron element of Fe-chlorin e6-Na, being tightly encased in the molecule, did not participate in the Fenton reaction. The SOD mimetic activity of FeCNa was stable against physico-chemical treatment such as pH shock, heat and digestion by pronase. For cancer bearing rats with oxidative stress (OS), immediate relief of OS was possible by a single intraperitoneal injection of FeCNa and relief continued for 24 hours. The subsequent administration of FeCNa suppressed cancer growth in vivo.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 2","pages":"139-45"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18667921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Zarkovic, M H Tillian, J Schaur, G Waeg, M Jurin, H Esterbauer
{"title":"Inhibition of melanoma B16-F10 growth by lipid peroxidation product 4-hydroxynonenal.","authors":"N Zarkovic, M H Tillian, J Schaur, G Waeg, M Jurin, H Esterbauer","doi":"10.1089/cbr.1995.10.153","DOIUrl":"https://doi.org/10.1089/cbr.1995.10.153","url":null,"abstract":"<p><p>Since a gradual benign-to-malignant progression of murine melanoma B16 after exposure in vitro to hypoxia was described recently, the aim of this study was to test if exposing melanoma B16-F10 cells to aldehyde 4-hydroxynonenal (HNE), which is considered not only as one of the major \"second toxic messengers\" of oxygen free radicals (or oxidative stress), but as a normal constituent of many cells and tissues, might have opposite effects. Treatment of the tumor cells with 50 microM HNE in vitro or in vivo did not prevent development of the tumors, but inhibited their growth. Tumor growth inhibition was equal for in vitro and in vivo treatment, but appeared after a delay of almost one week, since there was no difference of the tumor volume to the control observed during the initial period of the tumor growth. Similarly, both HNE treatment of the tumor cells before transplantation and HNE treatment of the melanoma bearing mice resulted in equally prolonged survival time. Thus, the results obtained suggest that while hypoxia could increase the malignancy of the murine melanoma cells, exposing these cells to one of the major \"second toxic messengers\" of oxygen free radicals, HNE, has almost opposite effects and further indicate the possible use of the aldehyde in vivo.</p>","PeriodicalId":79322,"journal":{"name":"Cancer biotherapy","volume":"10 2","pages":"153-6"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cbr.1995.10.153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18667882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}