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1.
Article in English | MEDLINE | ID: mdl-11740478

ABSTRACT

Four human immunodeficiency virus-positive homosexual men with 2- to 4.5-year histories of recurrent oral warts that had failed to respond to conventional surgical and other treatment modalities were offered treatment with interferon-alpha. All had multiple or large oral warts, 3 had skin warts, 2 had a history of anal warts, and 1 had penile lesions. All 4 patients were treated with a combination of intralesional and subcutaneous interferon-alpha. Adverse side effects were dose-related, mild, and transient; they included flulike symptoms (3 patients), hair loss and tachycardia (1 patient), and transient changes in the white blood cell count. All patients responded to therapy and remained free of disease up to 42 months. Intralesional injection with interferon-alpha appears to provide excellent clinical control for recurrent, multiple, and extensive oral warts in the human immunodeficiency virus-positive population, and is a useful adjunct to initial surgical removal of oral warts.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antiviral Agents/administration & dosage , Interferon Type I/administration & dosage , Mouth Diseases/drug therapy , Warts/complications , Warts/drug therapy , Adult , Homosexuality, Male , Humans , Injections, Intralesional , Injections, Subcutaneous , Male , Middle Aged , Mouth Diseases/complications , Recombinant Proteins
2.
J Clin Oncol ; 15(3): 1094-103, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9060550

ABSTRACT

PURPOSE: Patients with AIDS-related lymphoma usually have extensive lymphomatous disease, with relatively frequent involvement of the CNS. Approximately half may achieve complete remission after chemotherapy. Mitoguazone, an inhibitor of polyamine biosynthesis, has demonstrated efficacy in patients with de novo recurrent lymphoma. The drug is relatively nonmyelotoxic and may cross the blood-brain barrier. The current study was designed to assess the safety and potential efficacy of mitoguazone in patients with relapsed or refractory AIDS-lymphoma. PATIENTS AND METHODS: Thirty-five patients were accrued, all of whom had failed one (51%) or multiple (two to six) prior regimens. Mitoguazone (600 mg/m2) was given intravenously on days 1 and 8, and then every 2 weeks, until best response, progression, or toxicity. RESULTS: The median age was 39 years. High-grade lymphoma was diagnosed in 29 patients (83%). Extranodal disease was present in 30 patients (86%), with multiple extranodal sites (two to seven) in 18 (51%). The median CD4 cell count at study entry was 66/dL (range, zero to 549). Twenty-six patients were assessable for response. The objective response rate was 23% (95% confidence interval [CI], 6.9 to 39.3), with complete remission in three patients (11.5%), and partial remission (PR) in three patients (11.5%). Six patients experienced stable disease. Median survival from study entry was 2.6 months for the group as a whole; 21.5 months (range, 3.8 to 29.1) in complete responders, 5.6 months (range, 3.8 to 34.8) in partial responders. The most common toxicities occurred solely during drug infusion and included vasodilation (63%), paresthesia (86%), and somnolence (17%). Fourteen patients (40%) experienced nausea and 16 (46%) vomiting (grade 3 in one). Ten patients (29%) developed stomatitis, including grade 3 in two and grade 4 in one. Seven patients (20%) developed neutropenia, with grade 4 in one. Thrombocytopenia occurred in nine patients (26%). While on study, three patients developed sepsis, four had pneumonia, and two developed opportunistic infections. CONCLUSION: Mitoguazone is an effective agent in patients with multiply relapsed or refractory AIDS-related lymphoma, with acceptable toxicity. Further study in patients with newly diagnosed disease is warranted.


Subject(s)
Antineoplastic Agents/therapeutic use , Lymphoma, AIDS-Related/drug therapy , Mitoguazone/therapeutic use , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Mitoguazone/adverse effects , Neutropenia/chemically induced , Recurrence , Remission Induction , Survival Analysis , Thrombocytopenia/chemically induced
3.
J Clin Oncol ; 14(8): 2353-64, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8708728

ABSTRACT

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Daunorubicin/administration & dosage , Sarcoma, Kaposi/drug therapy , Adult , Alopecia/chemically induced , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Canada , Daunorubicin/adverse effects , Daunorubicin/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Carriers , Female , Humans , Liposomes , Male , Middle Aged , Neutropenia/chemically induced , Prospective Studies , Remission Induction , Sarcoma, Kaposi/etiology , Sarcoma, Kaposi/mortality , Survival Rate , Treatment Failure , United States , Vincristine/administration & dosage , Vincristine/adverse effects
4.
Biochem J ; 269(2): 381-8, 1990 Jul 15.
Article in English | MEDLINE | ID: mdl-2167067

ABSTRACT

We are attempting to develop methods for the sequencing of glycosaminoglycans from their reducing end. Here we describe a procedure for the analysis of dermatan sulphate from pig skin. The glycosaminoglycan is released from its parent proteoglycan by exhaustive proteolysis by using both endo- and exo-peptidases. The amino group of the residual serine residue is conjugated with a p-hydroxyphenyl group, which in turn is iodinated with 125I (the Bolton-Hunter reagent, BHR). The ion-exchange-purified end-labelled dermatan sulphate is then degraded partially or completely by various enzymic or chemical means to yield fragments extending from the labelled serine residue to the point of cleavage. The various products are separated by gradient PAGE, detected by autoradiography and quantified by videodensitometry. Complete digestion with chondroitin ABC lyase affords the labelled fragment delta HexA-GalNAc(-SO4)-GlcA-Gal-Gal-Xyl-Ser(-BHR). The structure was confirmed by sequential degradation from the non-reducing end by chondroitin AC lyase, HgCl2, and beta-galactosidase. Periodate oxidation cleaves most of the Xyl even without treatment with alkaline phosphatase, showing that Xyl is not substituted with phosphate. Results from partial and selective periodate oxidation indicate that most of the non-sulphated IdoA residues are located towards the non-reducing end. Partial or complete digestions with testicular hyaluronidase (in the presence of an excess of beta-glucuronidase) or chondroitin AC lyase identify the positions of GlcA residues. The results confirm that HexA next to Gal is always GlcA. Moreover, GlcA is common in the first three disaccharide repeats. Results with testicular hyaluronidase indicate that the distribution of clustered GlcA-GalNAc repeats is periodic and peaks at positions 1-3, 8-9 and around 25. Although there must be chains that contain IdoA in nearly all of the available positions, regions that have not been fully processed during biosynthesis are markedly non-random.


Subject(s)
Chondroitin , Dermatan Sulfate , Skin/analysis , Animals , Carbohydrate Sequence , Chondroitin/analogs & derivatives , Chondroitin Lyases , Chromatography, High Pressure Liquid , Dermatan Sulfate/isolation & purification , Electrophoresis, Polyacrylamide Gel , Hyaluronoglucosaminidase , Iodine Radioisotopes , Male , Mercuric Chloride , Molecular Sequence Data , Oxidation-Reduction , Periodic Acid , Swine , Testis/enzymology , beta-Galactosidase
5.
J Clin Oncol ; 5(9): 1410-8, 1987 Sep.
Article in English | MEDLINE | ID: mdl-2442323

ABSTRACT

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Head and Neck Neoplasms/radiotherapy , Methotrexate/administration & dosage , Adult , Aged , Aged, 80 and over , Clinical Trials as Topic , Combined Modality Therapy , Female , Head and Neck Neoplasms/drug therapy , Humans , Male , Middle Aged , Random Allocation
6.
J Clin Oncol ; 5(6): 951-5, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3585449

ABSTRACT

Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Salivary Gland Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Pilot Projects , Salivary Gland Neoplasms/pathology
7.
J Biol Chem ; 260(27): 14722-6, 1985 Nov 25.
Article in English | MEDLINE | ID: mdl-2932448

ABSTRACT

We have treated bovine lung heparan sulfate with alkaline [3H]borohydride to end label the chains with [3H]xylitol. After subsequent periodate oxidation-alkaline elimination products were separated by gel permeation and ion exchange chromatography. The linkage region fragment expected to have 2 galactoses and 1 [3H]xylitol residue appeared in the tetra-/trisaccharide region after gel filtration and was bound to the anion exchange resin. A similar negatively charged fragment, expected to have 2 galactoses, 1 xylose and 1 serine, was isolated after periodate oxidation-alkaline elimination of unlabeled heparan sulfate. The negative charge was due to the presence of alkaline phosphatase-labile phosphate ester. The molar ratio of galactose:phosphate:xylose was 2.17:1.19:1.00. The phosphate ester was associated with the xylose/[3H] xylitol moiety as indicated by the formation of phosphoxylose/-xylitol by beta-galactosidase digestion of the phosphorylated trisaccharide. Furthermore, orcinol reactivity disappeared after periodate oxidation of the dephosphorylated trisaccharide. The phosphate ester must be located to C-2 of xylose/xylitol as the 1-3H radioactivity could be released by periodate oxidation when it was preceded by alkaline phosphatase treatment. It is estimated that almost every chain of heparan sulfate carries 2-phosphoxylose. It would be of interest to know if glycosaminoglycan chains that are artificially initiated onto exogeneous beta-D-xylosides also acquire the 2-phosphoxylose moiety.


Subject(s)
Chondroitin Sulfate Proteoglycans/analysis , Glycosaminoglycans/analysis , Heparitin Sulfate/analysis , Lung/metabolism , Pentosephosphates/analysis , Proteoglycans/analysis , Sugar Phosphates/analysis , Trisaccharides/analysis , Animals , Borohydrides , Carbohydrate Sequence , Cattle , Chromatography, Gel , Chromatography, Ion Exchange , Heparan Sulfate Proteoglycans
8.
Oncology ; 42(3): 141-3, 1985.
Article in English | MEDLINE | ID: mdl-3889759

ABSTRACT

30 patients with advanced metastatic gastric adenocarcinoma, having a measurable indicator lesion, were randomized (1:2) to receive (intravenously) either weekly 5-fluorouracil alone (15 mg/kg) or combination treatment with cyclophosphamide (20 mg/kg) given on day 1 and 5-FU (15 mg/kg) given weekly on weeks 2-5, beginning on day 8. The combination cycle was repeated at 6-week intervals. Although the toxic effects of therapy were similar in both arms, the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response (5-FU 18%, combination 16%) or improve the median survival of patients with advanced measurable gastric carcinoma (5-FU 4.4 months, combination 5.2 months). Patients with pretreatment weight loss greater than 10% had significantly (p less than 0.05) shorter median survival (2.8 versus 5.6 months) compared to patients without weight loss.


Subject(s)
Adenocarcinoma/drug therapy , Cyclophosphamide/therapeutic use , Fluorouracil/therapeutic use , Stomach Neoplasms/drug therapy , Aged , Body Weight , Clinical Trials as Topic , Cyclophosphamide/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Female , Fluorouracil/administration & dosage , Humans , Injections, Intravenous , Male , Middle Aged , Prognosis , Random Allocation
9.
Cancer Treat Rep ; 65(7-8): 697-8, 1981.
Article in English | MEDLINE | ID: mdl-6166375

ABSTRACT

Forty-two patients with inoperable stage III or IV head and neck epithelial tumors were entered in a phase I pilot study to evaluate the toxicity and efficacy of combined radiotherapy and bleomycin for advanced head and neck cancers. Twenty-three patients (52%) achieved complete remissions and 18 patients (42%) had greater than 50% regression. Most patients tolerated bleomycin at a dose of 5 units twice a week, with a full course of radiotherapy delivered at 1809 rads/day, 5 days/week. Although the complete remission rate appears to be higher than with radiotherapy alone and 13 of the 23 complete remissions (57%) lasted greater than 1 year, methods of prolonging the duration of remission need to be developed.


Subject(s)
Bleomycin/therapeutic use , Head and Neck Neoplasms/radiotherapy , Bleomycin/adverse effects , Drug Administration Schedule , Drug Evaluation , Head and Neck Neoplasms/drug therapy , Humans , Neoplasm Staging , Pilot Projects , Prognosis , Radiotherapy Dosage , Stomatitis/chemically induced
10.
Cancer ; 45(9): 2240-4, 1980 May 01.
Article in English | MEDLINE | ID: mdl-6991095

ABSTRACT

One hundred twenty-one patients with advanced measurable adenocarcinoma of the colon were randomized for treatment with intravenous 5-fluorouracil (IV 5-FU) alone, 15 mg/kg/week vs. cytoxan, 15 mg/kg/week IV, on day 1 and 5-FU, 15 mg/kg/week IV during weeks 2--5, repeated in a six-week cycle. Age, sex, performance status, and disease free intervals, were comparable in both arms. Response frequency was 11% for treatment with 5-FU alone and 10% for treatment with combination therapy. The median survival time was significantly greater in the 5-FU-alone arm (8.4 months vs. 5.6 months, P less than 0.05). In both arms, survival was correlated with the nadir white blood count (WBC) achieved during therapy (P less than 0.02). Fourteen patients had pretreatment WBC of greater than 12,000/mm3. None of them had fever, bone marrow involvement with tumor, or recognizable infection at study entry. The 14 patients had a median survival time of 2.3 months, significantly shorter than that of patients with normal pretreatment WBC (P less than 0.05). A pretreatment lymphocyte count was available for all patients. No association between this value and either response to chemotherapy or survival time was noted. These results support the superiority of 5-FU to the combination of 5-FU and cytoxan in the treatment of colon carcinoma, and point to the prognostic significance of the pretreatment WBC in this disease.


Subject(s)
Adenocarcinoma/drug therapy , Colonic Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Fluorouracil/administration & dosage , Clinical Trials as Topic , Cyclophosphamide/adverse effects , Diarrhea/etiology , Drug Therapy, Combination , Female , Fluorouracil/adverse effects , Humans , Leukocyte Count , Leukopenia/etiology , Male , Middle Aged , Nausea/etiology , Prognosis
11.
Cancer Treat Rep ; 63(3): 351-7, 1979 Mar.
Article in English | MEDLINE | ID: mdl-85493

ABSTRACT

Between February 1976 and June 1977, 15 patients with advanced inoperable squamous cell carcinoma of the head and neck were entered in a pilot study sponsored by the Radiation Therapy Oncology Group using combined radiotherapy and multidrug chemotherapy. Chemotherapy consisted of cyclophosphamide, vincristine, and bleomycin (during radiotherapy) and cyclophosphamide, methotrexate, and bleomycin (after radiotherapy). At the time of last followup or of death, the disease had been controlled at the primary site in eight of the 15 patients (53%), in the neck in 12 patients (80%), and in all sites in seven patients (47%). Followup time ranged from 2 to 24+ months with a median of 7 months. Acute toxic effects of the combined treatment, primarily enhanced radiation mucositis and infection, were severe, and three patients had fatal complications. Although the combination chemotherapy may have enhanced the tumor response to radiotherapy in some of these patients, treatment morbidity and complications were prohibitive for the treatment program to progress to a randomized trial.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Bleomycin/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Clinical Trials as Topic , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Evaluation Studies as Topic , Female , Head and Neck Neoplasms/drug therapy , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Neoplasm Metastasis , Pilot Projects , Vincristine/therapeutic use
13.
Cancer ; 27(2): 308-13, 1971 Feb.
Article in English | MEDLINE | ID: mdl-5100393
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