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Biomedical subjects

C Plager

Publications and source records attributed to C Plager.

At least 73 records · Page 4Linked to original sources
PubMed1989

Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study.

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Ectopic production of the beta-subunit of human chorionic gonadotropin in osteosarcoma.

Production of human chorionic gonadotropin by sarcomas is an uncommon phenomenon that has rarely been documented. A case of a 26-year-old woman with osteosarcoma of the left fibula and high levels of serum beta-human chorionic gonadotropin (beta-HCG) is described. Immunoperoxidase staining showed numerous tumor cells reacting with the beta-HCG antibody. Immunohistochemical studies performed on ten additional osteosarcomas demonstrated another case in which some tumor cells presented immunoreactivity for beta-HCG. These results indicate that beta-HCG may be used as a marker of persistent or recurrent disease in those uncommon cases of osteosarcoma in which serum levels of beta-HCG are elevated at the onset of treatment.

Adult↗
PubMed1987

Comparison between clinical response and in vitro drug sensitivity of primary human tumors in the adhesive tumor cell culture system.

The newly described adhesive tumor cell culture system (ATCCS) offers a distinct advantage over other assays in that it has a high plating efficiency requiring low cell inoculum, it affords workable assays in approximately 70% of specimens from the heterogenous tumor types, and it has the ability to assay up to nine drugs at four different concentrations. Clinical correlations based on the ATCCS were obtained in 65 patients undergoing 71 clinical trials. Patients with melanoma, lung cancer, and sarcoma dominated the group. The most active in vitro drug was correlated per clinical trial. Thirteen of 17 (76%) sensitive in vitro predictions and 51 of 54 (94%) resistant in vitro predictions were accurate. The assay in this study had a sensitivity of 81% and specificity of 93%. These preliminary results are encouraging and warrant prospective trials to establish the true value of this assay to patients.

Adolescent↗
PubMed1987

Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules .

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.

Adolescent↗
PubMed1987

Osteosarcoma chemotherapy effect: a prognostic factor.

Chemotherapy has become a routine part of the treatment of osteosarcoma. However, the precise role of preoperative chemotherapy remains in question. Between 1979 and 1982, a group of 40 patients were treated by multimodality therapy consisting of preoperative chemotherapy (intra-arterial cis-platinum and systemic adriamycin), surgery, and postoperative chemotherapy. Survival in this group is 64%, while continuous disease-free survival is 58%. Although age, sex, tumor size, site, and classification were found to be prognostic factors, histologic evidence of response to preoperative chemotherapy, measured as percent tumor necrosis, was found to be the most significant prognostic factor. When continuous disease-free survival was calculated as a function of tumor necrosis it was 91% in patients with greater than or equal to 90% tumor necrosis, while it was 14% in patients with less than 90% tumor necrosis. At initial presentation, 7% of patients were judged limb-salvage candidates. But due to the local effects of preoperative chemotherapy, 60% ultimately underwent limb-salvage surgery. Preoperative arteriograms were a reliable means of monitoring response to chemotherapy and served as an indicator of residual viable tumor. Using arteriogram directed planes of section, postchemotherapy, specimens were "mapped" and analyzed for chemotherapy effect. When present, residual viable tumor was preferentially found at the interface of tumor and normal anatomic structures; "sanctuary sites." It is necessary that standard methods for analyzing postchemotherapy specimens be developed; a technique is described.

Bone Neoplasms↗
PubMed1986

Difluoromethylornithine and leukocyte interferon: a phase I study in cancer patients.

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-alpha) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-alpha was given in 100% increments ranging from 0.4 X 10(6)U/m2 to 3.2 X 10(6)U/m2 i.m. daily. At the fifth dose level both IFN-alpha and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-alpha/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+ weeks. Two additional patients had minor responses lasting 29 and 32+ weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.

Adult↗
PubMed1986

Initial clinical studies with copovithane.

Copovithane is a new copolymer of low molecular weight and with a significant in vivo antitumor activity in preclinical trials. The mechanism of action is unknown. Ninety-one patients with various metastatic neoplasms beyond the curable stage were treated with copovithane by weekly intravenous administration. Dose levels ranged from 1 to 33 g/m2/week. No dose-limiting toxicity was reached. Tolerance was excellent, with minor fatigue, occasional nausea, and intermittent proteinuria as the only significant side effects in less than 25% of patients. Two patients achieved a partial remission, and five patients reached minor responses during therapy. Antitumor effects were noted only in cutaneous and subcutaneous metastases. Extensive immunologic evaluation revealed some improvement in helper:suppressor T cell ratio, in vitro cytotoxicity tests, and lymphocyte blastogenic responses in patients treated at intermediate levels. The immunologic testing also suggested that the higher dose levels (22-33 g/m2 weekly) might adversely affect the immune response. The clinical relevance of these changes is uncertain. Phase II clinical trials are recommended utilizing weekly doses between 10 and 15 g/m2.

Adult↗
PubMed1986

Antibody development to viral and allogeneic tumor cell-associated antigens in patients with malignant melanoma and ovarian carcinoma treated with lysates of virus-infected tumor cells.

Pre- and postimmunization sera from six malignant melanoma and six ovarian carcinoma patients were used to investigate the humoral immune response to antigens expressed in extracts of allogeneic tumor cells and lysates of these same cells infected with virus. Nitrocellulose paper replicas of cell extracts, fractionated by polyacrylamide gel electrophoresis, were used as antigenic targets. Antibodies that bound to tumor cell antigens of defined molecular weight were identified with enzyme-linked probes specific for human immunoglobulins G, A, and M. Prior to therapy, all sera reacted with one or more antigens expressed by the unmodified tumor cells. Postimmunization sera from two malignant melanoma patients and one ovarian carcinoma patient reacted with antigens in extracts of uninfected tumor cells. These same antigens were not detected by preimmunization sera. Most postimmunization antibody responses were directed against antigens associated with the infecting virus itself and antigens found in extracts of virus-infected but not in extracts of uninfected tumor cells. These results suggest that treatment with lysates of virus-infected allogeneic human tumor cells elicits humoral immune responses against: (a) tumor cell-associated antigens; (b) antigens that are specifically virus associated; and (c) antigens that may be virus induced or virus modified cytoplasmic or nuclear antigens.

Allantois↗
PubMed1985

A phase II trial of PCNU in patients with malignant melanoma and central nervous system metastases.

Twelve patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with PCNU. All patients had prior chemotherapy and/or radiation therapy and had progressive brain metastases, documented by computerized tomography. PCNU was given as a single intravenous infusion of 90-110 mg/m2 every 6-8 weeks. There was one partial response and four patients had stable disease. Although no episodes of sepsis or bleeding occurred, seven of 17 courses led to significant granulocytopenia or thrombocytopenia. Nonhematopoietic toxicities were mild. These results indicate that systemic PCNU is unlikely to be more effective than other currently used chemotherapy in patients with malignant melanoma and CNS metastases.

Brain Neoplasms↗
PubMed1984

Phase-I trial of intracarotid BCNU and cisplatin in patients with malignant intracerebral tumors.

Eighteen patients with progressive or recurrent intracerebral malignant neoplasms after cranial radiation therapy were entered in a phase-I trial of intracarotid bis-chloroethylnitrosourea (BCNU) and cisplatin. Thirty-six courses of varying doses of BCNU and cisplatin were infused intraarterially via a percutaneous, trasfemoral approach. Courses were repeated every 4-6 weeks upon patients' recovery from toxicity. Intraarterial cisplatin or BCNU alone was administered if the blood counts were still subnormal. CT scans and neurologic examinations were performed monthly. Major toxic effects included ipsilateral retinal (amaurosis) in 4 patients and neurologic toxicity in 2 patients (minor focal seizure, reversible obtundation in one patient, and transient hemiparesis in one patient). One patient was infused by a catheter inserted into the supraclinoid internal carotid artery and had no further visual deterioration and no major side effects. Tumor regression was observed in patients previously treated with radiation and/or systemic chemotherapy, including 4 of 9 who had recurrent malignant gliomas, and 2 of 9 who had metastatic tumors. Recommended dose for phase-II trials is BCNU 100 mg/m2 and cisplatin 60 mg/m2 every 4-6 weeks. Retinal and neurologic toxicity are possible side effects.

Adult↗
PubMed1984

Phase II evaluation of PALA in patients with refractory metastatic sarcomas.

The efficacy of PALA was evaluated in 22 patients with metastatic soft tissue and bone sarcomas. The 20 evaluable patients had received a median of three prior chemotherapeutic regimens, including an adriamycin combination, to which eight had shown response. PALA was administered at 2-week intervals. Sixteen patients received 6 g/m2 over 1 hour intravenously as their initial dose, while six patients received 5 g/m2. The major side effects were skin rash, stomatitis, diarrhea, nausea, and vomiting. Significant myelosuppression was not seen. Two patients had stabilization of disease for periods of 10 and 13 weeks. At the dose and schedule used in this trial, PALA was not effective against advanced adult sarcoma.

Adult↗
PubMed1983

A randomized study of continuous infusion vindesine versus vinblastine in adults with refractory metastatic sarcomas.

A randomized study was conducted in 33 adult patients with refractory metastatic sarcomas to compare the therapeutic efficacy of continuous vindesine versus continuous vinblastine. Of 30 evaluable patients, 15 patients received vindesine as a continuous 5-day infusion at 1.2 mg/m2 repeated every 3 weeks, and 15 patients received vinblastine at 1.5 mg/m2/day every 3 weeks. Ten patients had stable disease, while 20 patients showed progressive disease. No objective responses were observed. There was adequate myelosuppression and both drugs were well tolerated with few catheter-related problems. It does not appear that vindesine or vinblastine, given by continuous 5-day infusion, is active in the treatment of metastatic sarcomas in adults.

Adult↗
PubMed1980

Ewing sarcoma: its course and treatment in 50 adult patients.

34 patients were treated for Ewing sarcoma with primary presentation. There were 10 females and 24 males with average age of 21 years (range 16-36 years). These patients received radiotherapy (greater than 5,000 R) to the primary site and combination chemotherapy with vincristine, cyclo-hosphamide, doxorubicin and actinomycin D. Of 19 patients with primary presentation in an extremity, 12 remain alive at 29 months without clinical evidence of tumor (63%); 2 patients are alive with relapse. All 10 patients with primary presentation in the pelvis died despite vigorous treatment. 3 patients are alive out of 5 patients with primary presentation in chest or abdominal wall or axilla but only 1 patient remained tumor-free. Of the entire group of 34 patients, 12 remained tumor-free at 27 months (35%). 2 relapsed patients were rendered surgically tumor-free and receive further treatment. 20 patients died or are receiving treatment for advancing disease. 16 patients were treated for locally recurrent (1 patient) or metastatic (15 patients) Ewing sarcoma. There were 6 females and 10 males (average age 24.7 years). These patients received palliative radiotherapy and combination chemotherapy with vincristine, cyclophosphamide, doxorubicin, actinomycin D and dacarbazine. At 36 months, 3 patients are alive tumor-free and 1 patient is alive with stable disease. 12 patients died, 2 after temporarily achieving complete remission.

Abdominal Neoplasms↗
PubMedDate not supplied

A phase II evaluation of bexarotene (Targretin) capsules in patients with metastatic melanoma.

A phase II study was undertaken to determine the efficacy of Bexarotene in melanoma. Between November 1997 and April 1998, 19 patients were given Bexarotene in single daily oral doses of 450 mg/m2 in capsule form continuously. Nineteen patients, four with choroidal metastatic melanoma, were treated. No responses were seen. Five patients had stable disease, two of the four with choroidal melanoma, had tumor progression. Myelosuppression was mild. Grade 3 myalgia, asthenia, diarrhea, cold hands/feet, and mood changes were seen in one patient each. Changes in serum triglyceride and thyroxine levels were common. Bexarotene, as used in this study, is not effective against melanoma.

Adult↗
PubMedDate not supplied

Cis-dichlorodiammineplatinum(II) in advanced soft tissue and bony sarcomas: a Southwest Oncology Group Study.

cis-Dichlorodiammineplatinum(II) (DDP), at a dose of 15 mg/m2/day x 5 consecutive days, was administered to 68 evaluable patients with metastatic soft tissue and bony sarcomas. All patients, except one, had received extensive prior chemotherapy and had had progressive disease at the start of the study. Responses observed included one complete response in a patient with mesothelioma and three partial responses in patients with soft tissue sarcomas (7%). No responses were seen in 18 patients with bony sarcomas. Significant leukopenia and thrombocytopenia were observed in less than 20% of evaluable courses, although two patients manifested life-threatening leukopenia (less than 1000 cells/microliter) and three had life-threatening thrombocytopenia (less than 24,000 cells/microliter). Nephrotoxicity was noted in less than 25% of evaluable courses. Nausea and/or vomiting was recorded in 55% of evaluable courses. DDP is considered to be marginally active in the secondary treatment of metastatic sarcomas at this dose and schedule. Further studies of DDP in mesothelioma are indicated.

Adolescent↗