摘要:

Induction chemotherapy followed by radiation has been extensively studied in an effort to improve local control and possibly overall survival of patients with locally advanced head and neck cancer. From June 1989 until May 1991, 39 patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy, consisting of cisplatin (100 mg/m2d 1) and Presented in part at the XV Congress of the European Society for Medical Oncology Copenhagen, 1990, p. 63, and at the ECCO-6 meeting, Firenze, 1991, p. 146. fluorouracil (1000 mg/m2d 2–6) followed by radiation potentiated by weekly administration of carboplatin (60 mg/m2). Surgery was performed in selected patients with residual disease after the combined modality approach. Four cycles of adjuvant chemotherapy with carboplatin (325 mg/m2) and bleomycin (15 u) were administered in those patients who demonstrated a partial response after locoregional treatment. There were 36 men and 3 women with a median age of 56 (range 39–74) years and Karnofsky performance status of 70 (range 60–100). The primary site of the tumor was nasopharynx (8), oropharynx (8), hypopharynx (3), oral cavity (4), larynx (13), paranasal sinus (2), and salivary glands (1). Thirty-two (82%) patients presentedwith stage IV disease. After the completion of induction chemotherapy, 14 (36%, 95% CI 21–53%) patients achieved a complete response (CR). This CR rate was increased to 56% (95% CI, 42–74%) after locoregional treatment. Main toxicities included nausea/vomiting (56%), leukopenia (40%), anemia (30%), thrombocytopenia (10%), stomatitis (28%), diarrhea (17%), and alopecia (12%). Median relapse-free survival was 18 (1–50) months, median time to progression was 13 (0.3–58.5) months, and median survival 19 (0.3–59) months. Induction chemotherapy with cisplatin and fluorouracil followed by radiation potentiated with carboplatin is feasible. However, this combined modality approach, as applied in the present study, does not appear to yield superior results than those reported with chemotherapy followed by radiation alone.

ISSN:0735-7907    

DOI:10.3109/07357909609012138

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The efficacy and toxicity of a combination of etoposide 100 mg/m2/day iv on day 2–4, leucovorin 300 mg/m2/day iv, and 5-FU 500 mg/m2day iv on day 1–5 every 4 weeks were assessed in 21 patients with advanced gastric cancer with measurable or evaluable diseases. Eight patients had an objective response, including 3 in CR. The overall response rate was 38.1% (95% CI 33.4–42.8%). Five of 8 patients who exhibited locally advanced and unresectable diseases had an objective response (2 CR, 3 PR). The response rate in patients with metastatic disease was 23.0% (95% CI 14.4–31.6%). The median progression-free interval and overall survival time were 7 and 10 months, respectively. The most frequent side effect was alopecia (Gr I/II 71.4%). No treatment-related death occurred. Modified ELF is a relatively effective and tolerable combination regimen for advanced gastric cancer and can be safely administered to elderly patients and patients with systemic diseases.

ISSN:0735-7907    

DOI:10.3109/07357909609012139

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

High-dose acetaminophen (HDAC) produces hepatocellular necrosis and cytotoxic changes in other tissues that express mixed-function-oxidase (MFO) activity. N-acetylcysteine (NAC), administered within 8 hr of HDAC exposure, replenishes reduced glutathione and prevents these effects. Numerous cell culture and animal studies have demonstrated that NAC may differentially protect normal cells compared with malignant cells from the toxic effects of chemotherapeutic agents and radiation. It was therefore proposed that HDAC with NAC rescue may be effective in malignancies that express MFO activity. To test this hypothesis, a phase I trial of HDAC with NA C rescue was conducted on 19 patients with advanced cancer. HDA C was escalated from 6 to 20 g/m2PO using a standard IV NAC rescue regimen. A total of 78 treatments were administered. Moderate fatigue, anorexia, and weight loss were the main toxicities observed. Transient grade 3 liver toxicity was noted following 1 treatment. Alopecia and renal and hematological toxicities were not observed. Responses after 4 courses administered weekly were as follows: response in at least 1 site—8 (partial 3, improved 3, mixed 2); stable disease—3; progressive disease—3; inevaluable—5. In conclusion, HDAC was tolerated with moderate fatigue, anorexia, and weight loss but few other effects using a standard IV NAC rescue regimen. A maximum tolerated dose was not reached at 20 g/m2. A 3/19 (15.8%) partial response rate was observed.

ISSN:0735-7907    

DOI:10.3109/07357909609012140

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The purpose of the study was to produce human monoclonal antibodies (hMcAb) against human colon cancer for use in radioimmunoimaging. Human-mouse heterohybridomas were developed by fusing SHM-D33 mouse-human hybrid heteromyeloma cells with human lymphocytes from colon cancer tumor-draining lymph nodes. The hybridomas capable of secreting human monoclonal antibodies were screened by using human colon cancer cell lines and pathological biopsies with ELISA and immunohistochemical methods. hMcAb clone H11 was selected for a large-scale antibody production, which was purified from mouse ascites. Biodistribution study demonstrated that specific uptake of125I-hMcAb H11 by human colon cancer xenografts was significantly higher than by normal tissues. Radioimmunoimaging of human colon cancer xenografts exhibited distinct tumor visualization during the period of 72–96 hr after intraperitoneal injection of125I-hMcAb H11. The development of human monoclonal antibodies such as hMcAb H11 may be useful for radioimmunodetection and therapy of colon cancer.

ISSN:0735-7907    

DOI:10.3109/07357909609012141

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Thymidine (dThd) has been shown to increase the activity of BCNU in mice, possibly due to its ability to inhibit poly(ADP-ribose)polymerase (PADPRP), an enzyme thought to be active in DNA repair. The present phase I study characterized the pharmacokinetics and toxicity of dThd combined with BCNU. Sixty patients with refractory malignancies were infused with escalating doses of dThd from 7.5g/m2/day to 105.5 g/m2/day for 48 hr, along with 100 mg/m2/day of BCNU for 2 doses. Further dose escalation of dThd was limited by large fluid volumes required; therefore, the BCNU dose was escalated to a maximum of 160 mg/m2/day for 2 days. Plasma dThd concentrations were determined using high-performance liquid chromatography. At doses above 37.5 g/m /day, steady-state concentrations of dThd approached or exceeded 1 mM, a concentration that nearly completely abolished BCNU-induced PADPRP activity in preclinical studies. Myelosuppression was consistent with BCNU dose but was not apparently increased by the coadministration of dThd. One patient had a partial response to therapy. Both the lack of effect of increasing dThd doses on BCNU-induced myelosuppression and the low response rate suggest that the schedule of drug administration was not optimal to inhibit PADPRP, or that PADPRP may not be essential in repairing BCNU-mediated DNA damage in humans.

ISSN:0735-7907    

DOI:10.3109/07357909609012142

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Cluster outbreaks of lymphoma and leukemia have been associated with viral infections in many species including humans, cattle, and cats. This study describes epidemiological, clinical, and pathological features of cluster outbreaks of lymphoma in multiferret households and examines and compares the Aleutian disease virus (ADV) and feline leukemia virus (FeLV) status of cases, ferrets at risk, and controls. Three ferret groups with 21 cases of histologically diagnosed lymphoma (12.6% cumulative incidence) and their cohabitants (n = 35) were examined and compared with three control groups (n = 52) of cohabitating ferrets without lymphoma. A familial distribution was observed in one group but most cases were not consanguinous. Ferrets greater than 3 years of age developed chronic disease in two of the groups and 2-year-old adults had acute disease in the remaining group. Lymphocytosis, splenomegaly, and lymphadenopathy were prominent features. Histologically, predominantly small noncleaved cell and polymorphous lymphoid lesions were observed. All of the ferrets with lymphoma that were tested for ADV and FeLV using serology or PCR were negative. The rate of ADV antibody among cases or ferrets at risk was not significantly different from controls. None of the cluster ferrets were seropositive for FeLV p27 antigen using a monoclonal ELISA. Infection with a novel ferret virus is suspected, but an etiological agent has not yet been identified.

ISSN:0735-7907    

DOI:10.3109/07357909609012143

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

The intactness of monocyte function in chronic myeloid leukemia (CML) patients as assessed by their ability to secrete tumor necrosis factor was evaluated. Monocytes from CML patients continued to respond to lipopolysaccharide (LPS) stimulation even during the refractory period, suggesting different pathways for stimulation by LPS and malignant processes.

ISSN:0735-7907    

DOI:10.3109/07357909609012144

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

In a phase II trial, 36 patients with advanced gastrointestinal cancer were treated with: folinic acid (FA) 500 mg/m2in a 2-hr intravenous (IV) infusion, 5-fluorouracil (5-FU) 600 mg/m2as an IV push injection 1 hr after FA, and hydroxyurea (HU) 35 mg/kg/day given p.o. in three administrations (every 8 hr) 6 hr after 5-FU. Cycles consisted of six weekly treatments for 6 weeks, followed by a 2-week rest period. Thirty-three patients were evaluable for response and 36 for toxicity; 73% had previous chemotherapy. The response rate was 30% (CR + PR), the median duration of response was 21 weeks (range 5–36), and time to failure was 17 weeks (range 3–51). The response in patients previously exposed to chemotherapy was 29% and 44% in chemotherapy-naive patients. The median survival for all entered patients was 28 weeks (range 6–54). The most common toxicity was gastrointestinal: diarrhea 22/36 (61%), mucositis 15/36(42%), and nausea and vomiting 15/36(42%); hematological toxicity was mild. We conclude that HU can potentiate the activity of 5-FU plus FA in advanced gastrointestinal cancer; in particular, HU can restore the activity of 5-FU in patients previously exposed to chemotherapy.

ISSN:0735-7907    

DOI:10.3109/07357909609012145

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Twenty patients with advanced sarcomas entered a pilot study with ifosfamide (IF) and mercaptoethane sulfonate sodium (Mesna) as a second-line treatment for six planned cycles. All patients had received prior doxorubicin- and cyclophosphamide-based chemotherapies. IF was administered at a dose of 3 g/m2given as continuous intravenous infusion for 24 hr on day 1–5 with Mesna. In the absence of disease progression, chemotherapy was planned to be repeated every 4 weeks for six consecutive cycles. Following chemotherapy, only 2 patients (11%) achieved partial response with response durations of 6 and 9 months. There was no complete response. When considered for only high-grade tumors, the response rate reached up to 22%. Toxicity was reported for 48 cycles and the dose-limiting toxicities were myelosuppression (22%) and encephalopathy (17%). Chemotherapy protocol was changed after two or three courses in 16 patients with stable or progressive diseases. IF/Mesna chemotherapy at this dose and schedule was not found to be very promising in refractory sarcomas as a second-line chemotherapy.

ISSN:0735-7907    

DOI:10.3109/07357909609012146

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609012147

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor