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PubMed1998

[SMANCS-TAE combined with PEI in the treatment for hepatocellular carcinoma].

From January 1996 to August 1997, 24 patients with advanced hepatocellular carcinoma (HCC) equal to or more than 2 cm (mean +/- SD; 4.1 +/- 3.0 cm) in main tumor diameter were treated by SMANCS-TAE (20 cases) or SMANCS-TAI (4 cases) combined with PEI. Six cases had solitary lesion, 16 cases had multiple lesions, and 2 cases had massive lesions. After this combination therapy, 21 of 24 cases had complete tumor necrosis. During 3 to 19 months follow up period, 12 cases had cancer-free survival (SMANCS-TAI; 3 cases), and 9 cases had tumor recurrences (3 cases were local recurrences and 6 cases involved new lesions). Two cases died of hepatic infarction and cancer death, however, the remaining 22 cases were surviving. SMANCS-TAE combined with PEI is useful treatment for advanced large or multiple HCC lesions in patients who are poor surgical risks.

Aged↗
PubMed1998

Therapeutic options for the treatment of colorectal cancer following 5-fluorouracil failure.

Therapeutic options after failure of 5-fluorouracil (5-FU) for the treatment of colorectal cancer include regional treatments, different 5-FU-based regimens, and different chemotherapy regimens. Of the regional treatments, resection of hepatic metastases is the most satisfactory because of the potential for long-term survival; however, the number of candidates for this option is limited. Responses are possible if 5-FU is administered by prolonged infusion, but the addition of other chemotherapeutic agents (eg, nitrosoureas, mitomycin C, or cisplatin) is less likely to induce objective responses. The new topoisomerase I inhibitor irinotecan has promising activity in patients with metastatic colorectal cancer. Depending on the status of the patient population, objective response rates of 15% to 30% have been reported in patients with colorectal cancer that has progressed or rapidly recurred following 5-FU-based treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A review of topical and intralesional cidofovir.

Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency Syndrome (AIDS). It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or by intralesional injection in several virally induced cutaneous diseases. Available information demonstrates that cidofovir is a potent antiviral agent with activity against several DNA viruses that cause cutaneous disease when applied topically or administered by intralesional injection. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in animals and a limited number of patients including those infected with human immunodeficiency virus (HIV). This article reviews the pharmacology of cidofovir and the utility of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir resistant strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and monkeypox.

Administration, Topical↗
PubMed1998

Topical and intralesional cidofovir: a review of pharmacology and therapeutic effects.

BACKGROUND: Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or intralesionally in several virally induced cutaneous diseases. OBJECTIVE: Our purpose was to review the usefulness of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir-resistant strains), Kaposi's sarcoma-associated herpesvirus, and molluscum contagiosum. METHODS: We performed a review of recent literature. RESULTS: Cidofovir is a potent topical intralesional antiviral agent with activity against several DNA viruses that cause cutaneous disease. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. CONCLUSION: The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in a limited number of patients including those infected with HIV. Although larger studies will be necessary to determine the specific function that topical cidofovir will have in the treatment of cutaneous diseases caused by DNA viruses, the drug offers significant promise.

AIDS-Related Opportunistic Infections↗
PubMed1993

Immunotherapy with intralesional and systemic interleukin-2 of patients with non-small-cell lung cancer.

Eight patients affected by non-small-cell lung cancer were treated with intralesional and systemic recombinant IL-2 (rIL-2) injection with the aim of activating both tumour-infiltrating lymphocytes and circulating cytotoxic or killer cells. The schedule of treatment was as follows: a daily fine-needle transparietal intralesional rIL-2 injection (1 x 10(5) Cetus units) from day 1 to day 5 and systemic rIL-2 infusion (1 x 10(5) Cetus units kg-1 day-1) from day 6 to day 10. One to four cycles of treatment were received by each patient. Clinical and immunological evaluations were performed (a) before treatment, (b) following the intralesional rIL-2 administration, (c) 1 h after the beginning of rIL-2 infusion and (d) at the end of the systemic rIL-2 infusion. No complete remission was achieved, two patients showed a partial remission, three resulted in stable disease and three patients progressed. Natural killer and lymphokine-activated killer cell activity dramatically decreased 1 h after the beginning of rIL-2 infusion and increased at the end of treatment. A progressive increase of circulating CD8+ and HLA class II+ T cells as well as of CD8+ T cell clones, most of which displayed NK activity, was recorded following rIL-2 infusion. Present data indicate that (a) the local administration of rIL-2 coupled with systemic rIL-2 infusion may be suggested as an alternative approach for the immunotherapy of lung cancer, (b) rIL-2 induces different immunological modifications according to the route and the time of its administration and (c) rIL-2 administration increases the amount of circulating immune cells with potential antitumour activity.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Variation in modes of chemotherapy administration for breast carcinoma and association with hospitalization for chemotherapy-related toxicity.

BACKGROUND: To the authors' knowledge, few studies to date have addressed the patterns of how chemotherapy was administered (administration modes) over time. In the current study, the goal of the authors was to describe how chemotherapy for breast carcinoma was administered and to determine whether chemotherapy administration modes were associated with toxicity in a community-based large cohort. METHODS: The authors studied 5256 women who were diagnosed with breast carcinoma at age 65 years or older between 1992-1999 and received chemotherapy. The patients were identified from the Surveillance, Epidemiology, and End Results (SEER)Program-Medicare linked databases. Chemotherapy drugs and modes of administration were determined through procedure codes in Medicare claims. RESULTS: Of the 5256 patients who received chemotherapy, 33% received it through an intravenous infusion for less than 1 hour; 39% through an intravenous infusion lasting 1-8 hours; 15% through an intravenous infusion lasting longer than 8 hours and requiring a pump; 12% through an intravenous push technique; and 1% through a subcutaneous, intramuscular, or intralesional injection. These modes varied substantially across the 11 SEER areas. The risks of hospitalization for chemotherapy-related toxicities (neutropenia, fever, thrombocytopenia, and adverse effects of systemic therapy) were not found to be significantly associated with different modes of chemotherapy after adjusting for other factors. Compared with patients receiving 5-flurouracil using an intravenous infusion for longer than 8 hours, the risk of toxicity was determined to be 0.96 (95% confidence interval [95% CI], 0.63-1.47) for patients treated with an intravenous infusion lasting 1-8 hours; 0.94 (95% CI, 0.62-1.41) for patients treated with an intravenous infusion lasting less than 1 hour; and 0.66 (95% CI, 0.38-1.08) for patients treated with subcutaneous, intramuscular, or intralesional injection or an intravenous push technique. CONCLUSIONS: There were substantial geographic variations noted in the modes of administering chemotherapy; however, these variations did not appear to be associated with the risk of toxicities (neutropenia, fever, thrombocytopenia, and adverse effects of systemic therapy).

Aged↗
PubMed2003

Percutaneous puncture and pre-operative cyanoacrylate obliteration of a traumatic false aneurysm of an angular artery branch.

We report a case of traumatic false aneurysm developed in the right glabella in a 5-year-old boy 3 weeks after an innocuous fall. Ultrasound, CT and facial arteriography did not reveal the feeding artery. After direct puncture of the glabellar bulge and rapid aspiration of blood, percutaneous contrast agent infusion revealed that the false aneurysm was supplied by the contralateral angular artery. Intralesional obliteration with cyanoacrylate was subsequently performed smoothly. Succeeding excision was easy and the cosmetic outcome was excellent.

Accidental Falls↗
PubMed1992

A case of linitis plastica of the rectum treated by pelvic exenteration after aggressive immunochemotherapy.

Multidisciplinary treatment was administered to a 32 year-old man with primary linitis plastica of the rectum, which was considered inoperable due to an extensive local spread at the first operation. Thirty KE of OK-432 was injected into the tumor per week (total 90-KE) and 5 KE of OK-432 was inoculated into the intracutaneous space per week (total 125 KE). Also methotrexete (MTX 50 mg) and 5-FU (500 mg) combined were given each week by intra-arterial infusion (total 20 courses). After this immuno-chemotherapy the CEA decreased from the pretreatment value of 12.7 ng/ml to 3.6 ng/ml and the tumor size was reduced. A total pelvic exenteration could then be performed almost curatively. As a result, this patient was able to return to the society with a better quality of life and has survived for 20 months since presentation.

Adult↗
PubMed2006

Suppression of tumor growth using a recombinant adenoviral vector carrying the dominant-negative mutant gene Survivin-D53A in a nude mice model.

Survivin (SVV), an inhibitor of apoptosis protein, is found to be upregulated in many cancers. We previously demonstrated that a dominant-negative mutant SVV-D53A was able to induce apoptosis in a p53-independent manner. Here, we report the construction and characterization of a recombinant replication-deficient adenoviral vector encoding a human SVV-D53A gene for its effectiveness against tumor growth both in vitro and in vivo. Transfection of liver tumor cells QGY-7703 with Ad-SVV-D53A results in significant apoptosis as measured by an increase in sub-G1 DNA content, procaspase-9 activation and further downstream PARP-1 cleavage. Furthermore, animal studies using QGY-7703 liver carcinoma xenografts in nude mice revealed that treatment of QGY-7703 cells with dominant-negative SVV-D53A, but not with wild-type SVV-adenovirus, prevents tumor outgrowth, inhibits growth of established tumors and results in a notably improved survival advantages in xenograft studies. Both the transferase-mediated dUTP nick-end labeling assay and immunostaining experiment demonstrated that tumor growth inhibition is associated with apoptosis induced by SVV-D53A expression. Taken together, these data suggest that recombinant adenovirus Ad-SVV-D53A carrying a Survivin dominant-negative gene SVV-D53A promotes apoptosis-mediated tumor suppression and could potentially be a promising candidate for cancer therapies.

Adenoviridae↗
PubMed1995

Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors.

Two murine monoclonal antibodies, BC-2 and BC-4, raised against tenascin and labeled with 131I were infused locally in the site of neoplastic disease by means of a removable (16 patients) or indwelling (34 patients) catheter. Fifty patients bearing a malignant glioma were treated. Twenty-six of these were suffering from recurrent disease; their tumors relapsed within 9 months (median) after treatment. The remaining 24 cases had a newly diagnosed tumor, and local radioimmunotherapy (RIT) was given immediately after surgery and radiochemotherapy. All efforts were made to reduce the tumor before the infusion of the radiopharmaceutical. Therefore, 22 cases with relapsing glioma underwent additional debulking surgery, which led to total or subtotal removal of tumor in 9 of the patients. Altogether, 28 patients had intralesional RIT when the disease was minimal or microscopic. Conversely, 22 cases underwent local RIT with a tumor the diameter of which was > 2 cm. In many cases, the infusions were repeated up to six times to achieve complete destruction of the neoplastic tissue. The local treatment did not give rise to systemic or to cerebral adverse effects. The labeled monoclonal antibodies, given directly in the site of the lesion, concentrated in very high amount in the neoplastic tissue and remained fixed in the target for a long period of time. For these reasons, the radiation dose to the tumor was remarkable (on average > 30,000 cGy/cycle) and consequently led to promising results. The median survival was, in total, 20 months (18 in recurrent tumors and 23 in newly diagnosed lesions). Moreover, median survival was 17 months in patients with bulky tumors (both recurrent and newly diagnosed tumors) and 26 months in patients with minimal or microscopic disease. The median time to progression was 3 months in recurrent and 7 months in newly diagnosed gliomas. Finally, RIT produced 3 CRs (all in recurrent tumors), 6 PRs (4 in recurrent and 2 in newly diagnosed), and 11 stabilizations of disease (4 in recurrent and 7 in newly diagnosed). In 19 cases (13 recurrent and 6 newly diagnosed) the progression of tumor was recorded. Eleven patients (2 recurrent and 9 newly diagnosed) who were treated by RIT when their disease was minimal and nondetectable by radiological methods remained disease-free and were classified as NED. The overall response rate (NED plus CR plus PR) was 40% (34.6% recurrent and 45.8% newly diagnosed).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas].

Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.

Antineoplastic Agents↗
PubMed1993

Administration of pentosan polysulfate to patients with human immunodeficiency virus-associated Kaposi's sarcoma.

BACKGROUND: Neovascularization induced by basic fibroblast growth factor (basic FGF) or FGF-like cytokines is thought to play a substantial role in the pathogenesis of human immunodeficiency virus (HIV)-associated Kaposi's sarcoma. Pentosan polysulfate has been shown to inhibit basic FGF and FGF-like dependent tumor growth both in vitro and in vivo. Moreover, it has been found to inhibit the growth of Kaposi's sarcoma-derived spindle cells in vitro. These observations suggested that pentosan polysulfate might be worth exploring as a potential agent for the treatment of Kaposi's sarcoma. PURPOSE: The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm. METHODS: Sixteen HIV-seropositive patients with Kaposi's sarcoma received pentosan polysulfate via continuous venous infusion for 3-6 weeks and then received a subcutaneous dose three times per week. Three different doses of pentosan polysulfate were administered: 2 mg/kg per day by infusion followed by 2 mg/kg per dose given subcutaneously (six patients), 3 mg/kg per day by infusion followed by 3 mg/kg per dose given subcutaneously (five patients), and 4 mg/kg per day by infusion followed by 4 mg/kg per dose given subcutaneously (five patients). Five of the 16 patients in the study also received injections of 1 mg of pentosan polysulfate into two different lesions two times a week for 3 weeks, followed by intralesional therapy once weekly. After receiving pentosan polysulfate for 6 weeks, patients were administered 100 mg zidovudine (AZT) orally every 4 hours in conjunction with pentosan polysulfate. RESULTS: The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day. No patient had an objective clinical antitumor response to either systemic or intralesional pentosan polysulfate administration; however, three patients had stable Kaposi's sarcoma for 3-27 weeks. No statistically significant effect on CD4 cells or serum HIV p24 antigen was noted during pentosan polysulfate administration. Dose-limiting toxic effects were characterized by anticoagulation and thrombocytopenia and were reversible. CONCLUSION: Pentosan polysulfate was well tolerated in this patient population. However, no objective tumor response or evidence of anti-HIV activity was noted; therefore, no claim of activity can be made in this trial. IMPLICATION: Continued investigation into the use of angiogenesis inhibitors with improved activity and toxicity profiles or different mechanisms of action is warranted.

Adult↗
PubMed1989

[Preoperative continuous intra-arterial infusion chemotherapy as part of a local regional treatment of osteosarcoma of the extremities].

Preoperative continuous intra-arterial chemotherapy combined with surgery in the treatment of osteosarcoma has been since 1968 in our clinic. Sixty-three cases with osteosarcoma of the extremities were evaluated in this study. Eighteen of these cases underwent limb salvage procedures. There were three intralesional, eleven marginal and four wide excision cases. From the standpoint of local failures, there were only two recurrent cases. One occurred after a marginal excision and the other after an intralesional excision. The 5-year cumulative survival rate for limb salvage cases was 56.0%, as compared with 40.6% of the amputation cases. Therefore we conclude that preoperative continuous intra-arterial infusion chemotherapy is a very effective method as a local regional therapy for osteosarcoma of the extremities.

Adolescent↗
PubMed1994

[Chemoimmunotherapy of malignancies of the gastrointestinal tract].

Stimulation of the immune response could be obtained in outpatients with inoperable locally advanced or metastasizing gastrointestinal tumors (n = 56), who were palliatively treated with cyclophosphamide (cy), 350 mg/m2 i.v., thymostimulin, echinacin i.m. and in part additionally with epirubicin, 15 mg/m2 i.v. At present, outpatients with pancreatic (n = 7) or colon carcinomas (n = 1) receive interleukin 2 (IL-2) intralesionally, 2 x 10(5) Cetus units (CU), days 3, 5 and 7 after cy, and by portable continuous infusion systems i.v., 3 x 10(5) CU/day, days 3-8 after cy. Subsets of lymphocytes slightly decreased in the patients' peripheral blood, recall antigen reactivity slightly increased. Patients' mean survival time was 5.7 +/- 1.7 months.

Cyclophosphamide↗
PubMed2003

SubTenon's infusion of steroids for treatment of orbital hemangiomas.

PURPOSE: To introduce an alternate technique for the treatment of infantile orbital hemangiomas. DESIGN: Non-comparative case series. PARTICIPANTS: Seven consecutive children with orbital hemangiomas. INTERVENTION: Posterior subTenon's steroid infusion using a blunt-tip cannula. MAIN OUTCOME MEASURES: Clinical stabilization, improvement, or resolution. RESULTS: Significant and sustained involution of the hemangiomas occurred in all cases. No local or systemic complications occurred. CONCLUSIONS: The results of subTenon's steroid infusion for the treatment of orbital hemangiomas in children are encouraging and may be associated with fewer intraoperative risks compared with direct intralesional injection.

Betamethasone↗