摘要:

Twenty patients with inoperable locally advanced Stage II and III pancreatic cancer were treated with combined modality therapy. Radiotherapy consisted of split courses of 2000 cGy each and, as needed, an additional 1400 cGy, separated by 2-week intervals. Simultaneous multidrug regimen chemotherapy consisted of 5-fluorouracil, continuous infusion, 1 g/m2days 1–5; streptozotocin, 300–500 mg/ m2days 1, 2, 3; and cisplatin, 100 mg/m2day 3 of every 4-week radiotherapy course (RT-FSP). Primary tumors decreased more than 50% in volume in II of 20 patients. Computed tomography scans demonstrated apparent complete disappearance of the primary tumor in 7 patients. Only 3 patients had tumor re growth within the radiotherapy field, all after the end of radiotherapy. Local control improved as measured by increased frequency of tumor shrinkage and decreased frequency of primary tumor growth, recognizing the limitations of a pilot study and comparisons to best historical results achieved with standard short 5-fluorouracil schedules and radiotherapy. Successful local control largely eliminates the most common cause of refractory pain and may decrease the need for some forms of early palliative surgical intervention. Tumor shrinkage sometimes downstages tumors, creating frequent investigational opportunities for either elective extirpative surgery or intraoperative radiotherapy. This pilot experience also supports testing of expanded eligibility staging criteria for combined modality treatment and testing of new drugs as part of 5-fluorouracil-radiotherapy-based regimens.

ISSN:0735-7907    

DOI:10.3109/07357909309024847

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

This phase I study of 36 patients was performed to identify the maximal tolerated dose of oral calcium leucovorin (CLV) that could be concomitantly administered with protracted 5-fluorouracil (5-FU) infusion (greater than 30 days). Administration of CLV in very small doses (5 mg p.o. q8h) with 5-FU, 200–300 mg/m2/day, resulted in excessive toxicity requiring treatment interruption in all patients. Subsequent reduction in the dose of 5-FU to 100 mg/ m2/ day with simultaneous administration of CLV, 5 mg p.o. q8h, decreased the toxicity and allowed for protracted administration of the combination. In subsequent patients the dose of oral CLV was increased to 22.5 mg p.o. q8h, which resulted in treatment-limiting toxicity in the majority of patients. Toxicity consisted almost exclusively of mucositis. No mye-losuppression or significant organ toxicity was observed. We conclude that even low doses of oral CLV potentiate the biological effect of infusion 5-FU. If the combination is to be given on a protracted basis, 5-FU must be administered at a much smaller dosage than has been traditionally utilized.

ISSN:0735-7907    

DOI:10.3109/07357909309024848

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The use of the enzyme tryptophan side-chain oxidase, isolated fromPseudomonas XA, was explored in 3 patients with refractory acute lymphocytic leukemia. Patients were given either a low-tryptophan diet or tryptophan-free hyperalimentation, prior to and during therapy. Their plasma, separated by pheresis, was continuously passed through a tryptophan depletion column containing the immobilized tryptophan side-chain oxidase. Up to 4 plasma volumes were passed through the column daily, 5 days per week for 2–3 weeks, and plasma tryptophan levels, both free and total, were measured by high-performance liquid chromatography. Pre-and postcolumn plasma samples were collected throughout the pheresis procedure. Ail postcolumn plasma samples had unmeasurable tryptophan levels throughout the treatment period, whereas precolumn samples were always measurable. Generally, tryptophan levels of plasma isolated from peripheral blood decreased after therapy, but rebounded by the next day. The enzyme depletion column reduces circulating plasma tryptophan levels, and its use is well tolerated by patients. However, further development of this method will require study of the effects of diet and of the duration, interval, and frequency of use of this column on therapeutic efficacy. Problems include difficulties with extended diet compliance and apparently intensive mobilization of tryptophan from body stores, which may preclude the clinical application of this enzyme depletion column.

ISSN:0735-7907    

DOI:10.3109/07357909309024849

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909309024850

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cisplatin continues to be one of the most commonly used cytotoxic agent. Problems of drug resistance and nephrotoxicity have generated interest in new platinum derivatives. In this study, we used flow cytometry to study their effects on cell kinetics and to see if the extent of cell cycle perturbations can be used to determine relative potency. The following four platinum derivatives were tested: cisplatin, carboplatin, 2543, and NK121 on two human ovarian cancer cell lines: BG1 and CAOV3. Flow cytometric analysis revealed a dynamic spectrum of cell kinetic perturbations, which included sequential S-G2 block, concomitant S-G2 block, and a dominant S block with abolition of G2 block. Platinum derivatives NK121, 254S, and CARBO induced an average of 54.5±5.6, 21.2±5.5, and 2.5±2.8% more S-G2 blocks than cisplatin, respectively. When comparing the severity of S-G2 blocks and requiring a p-value of 0.05, the order of increasing potency was: cisplatin, carboplatin, 2543, and NK121.

ISSN:0735-7907    

DOI:10.3109/07357909309024851

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

U-73, 975 (U-73), U-77, 779 (U-77), and U-80, 244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act us alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study wus designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 2 0.115 ng/ml; U-77, 0.650±0.209 ng/ml; U-80, 3.0±3.0 ng/ml; DDP, 4.40±2.83μg /ml; and DXR, 0.286±0.040μg /ml. U-73 appears the most potent analog, being 103to 104times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 102to 103greater potency than DDP and DXR. All the cervical, endometrial, und ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U-80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents.

ISSN:0735-7907    

DOI:10.3109/07357909309024852

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The combination of mitomycin-C and etopzoside showed synergistic cell kill effects in vitro against HEp-2 laryngeal squatnous carcinoma cells both in monolayer and in multicellular tumor spheroid systems. This cornbination was also synergistic in inhibiting HEp-2 tumors growing in nude mice. One course of this combination produced no complete regression of this tumor. When these two agents were combined with recombinant human granulocyte colony-stimulating factor (G-CSF) mutein, the doses of the drugs could be escalated approximately 1.5-fold higher than the doses that were tolerated without G-CSF support. With this modest close intensication, apparent cure MWS observed. High-dose mitomycin-C plus etoposide with G-CSF support may be useful, for the treatment of patients with inoperable squamous cell carcinoma of the head and neck.

ISSN:0735-7907    

DOI:10.3109/07357909309024853

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We have measured the clonogenic survival of cells isolated directly from colon cancer surgical specimens and treated with 5-fluorouracil (5-FU). Enzymatically dissssociated cells were incorporated into hybrid spheroids, consisting predominantly of nonproliferating HeLa feeder cells. Aliquots were exposed for 1.5 hr to a range of concentrations of 5-FU. From the decrease in clonogenic survival, as deduced from the frequency of colony formers among hybrid spheroids after chemical treatment, we were able to construct survival curves in 50% of the surgical specimens tested. A striking revelation was the presence of a resistant plateau in the survival curves, reminiscent of the solid tumor response to treatment with 5-FU. This resistance was absent in monolayer cultures. Evidence is presented that this resistance is due to the absence of, or delay in, cell cycle progression of cells residing in hybrid spheroids.

ISSN:0735-7907    

DOI:10.3109/07357909309024854

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter.Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors.

ISSN:0735-7907    

DOI:10.3109/07357909309024855

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

This is a case report of small cell lung cancer (SCLC) that underwent spontuneous regression. This was associated with severe neuropathy, which was unresponsive to therapy, including corticosteroids andplasmapheresis. We present here the case report and a brief review of the literature.

ISSN:0735-7907    

DOI:10.3109/07357909309024856

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor