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Biomedical subjects

G Schwartsmann

Publications and source records attributed to G Schwartsmann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Carcinomatous meningitis as a clinical manifestation of pancreatic carcinoma.

Carcinomatous meningitis (CM) is clinically less common than brain metastasis or spinal cord compression, having dire consequences for both the quality of life and the overall survival of patients with solid tumors. It occurs in about 5% of all adult cancer patients, but autopsies may double this number. If leukemia and lymphoma are excluded, most cases are due to breast cancer, lung cancer and melanoma. In this report, we describe a 49-year-old male patient with metastatic pancreatic adenocarcinoma who developed carcinomatous meningitis. To our knowledge, this is only the second case of carcinomatous meningitis secondary to a pancreatic carcinoma described so far.

Adenocarcinoma↗
PubMed2001

Cervical cancer screening in Porto Alegre, Brazil: alternative methods for detecting cancer precursors in a developing country.

OBJECTIVE: This study was conducted to test the performance characteristics of cervical cancer screening by visual inspection of the cervix with acetic acid and iodine solution. METHODS: A total of 100 women were screened for cervical cancer by Pap smear and naked eye inspection of the cervix after application of acetic acid and iodine solution. RESULTS: Comparing visual inspection to the Pap test, a sensitivity of 85.7%, specificity of 78.5%, and concordance of 79% (p < .0011) was established. Comparing the Pap test with colposcopy, the corresponding figures were 42.9%, 92.3%, and 66.6% (p < .077), respectively. Visual inspection compared to colposcopy showed corresponding figures of 100%, 7.7%, and 55.5% (p = .48), respectively. Colposcopy and biopsy had an agreement of 100%. CONCLUSIONS: Visual inspection with acetic acid and iodine solution proved to be a reasonable method of screening for cervical cancer precursors.

Journal Article↗
PubMed2001

Fractionated doses of oral etoposide in the treatment of patients with aids-related kaposi sarcoma: a clinical and pharmacologic study to improve therapeutic index.

The purpose of this study was to examine the antitumor activity, toxic effects, and plasma pharmacokinetics of fractionated doses of oral etoposide aiming at the achievement of prolonged safe and active plasma drug levels in patients with AIDS-related Kaposi sarcoma (KS). This was designed as a phase II trial in which consecutive patients with progressing AIDS-KS after at least 3 months of active antiretroviral therapy received oral etoposide at the dose of 20 mg/m2 every 8 hours daily for 7 days every 21 days, with the study of its plasma pharmacokinetics. Eligible patients were 18 to 60 years old, with a histopathologically confirmed diagnosis of AIDS-related KS, human immunodeficiency virus-positive test, progressing after at least 3 months of active antiretroviral therapy, World Health Organization (WHO) performance status 0 to 3, New York University staging IIA or greater, no active infection except oral candidiasis, normal bone marrow, liver, and renal function, and who signed an informed consent. Objective tumor responses were evaluated after at least one full treatment course according to a modified WHO criteria, and toxicity was evaluated weekly and graded using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) criteria. For the pharmacokinetic study, plasma was obtained from patients during the first drug administration immediately before and at various time points thereafter. Etoposide was measured after extraction from plasma by a standard high-performance liquid chromatography. Twenty-one patients were accrued for the study, and 18 of them met the eligibility criteria. They were all men, with median age of 36 years old (range: 25-50 years), median WHO performance status 0 (range: 0-3) median CD4+ count (cells/mm3) 67 (range: 8-443), prior AIDS diagnosis in 10 of 18 cases, NYU staging IIA (1 patient), IIB (1), IIIA (7), IIIB (1), IVA (4), and IVB (4) sites of disease: mucocutaneous only (5), mucocutaneous/lymph nodes (5), mucocutaneous/lung (5) and mucocutaneous/lymph nodes/lung (2); and prior cytotoxic treatment in two patients. Seventy-two percent of cases presented some form of toxic effect (NCI-CTC). Leukopenia was documented in 50% of cases, anemia occurred in 61%, whereas thrombocytopenia was documented in 17% of the patients. The main nonhematologic toxicities were nausea and vomiting in 17% of cases and alopecia in 44%. The overall objective response rate was 83%, with 2 complete remissions documented (11%). The median duration of responses was 12 weeks (range: 3-45 weeks). The median t1/2 of etoposide in plasma was 4.11 hours (range: 1.95-9.64), area under the curve was 13.51 microg/h/ml (range: 7.12-24.42), Cmax was 2.17 microg/ml (1.40-4.41), tmax (1.00-2.00), mean residence time 4.62 hours (range: 3.75-5.20 hours), CIt (total clearance) 3.13 l/m2/h (range: 1.49-5.20 l/m2/h), Vd 13.08 l/m2 (range: 6.23-19.65 l/m2), and the median etoposide plasma concentration time greater than 1 microg/ml was 3.69 hours (range: 1.00-6.80 hours). The use of fractionated oral daily doses of etoposide produced significant antitumor activity with manageable clinical toxicity in the individuals with AIDS-KS included in this trial. This more favorable therapeutic index of etoposide could be due to the achievement of more sustained plasma levels of the drug within safe but active concentrations.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Sentinel lymph node identification and sampling in women with early breast cancer using 99m Tc labelled dextran 500 and patent blue V dye.

The status of the homolateral axillary lymph nodes is still the most important prognostic factor in early stage breast cancer. The information obtained from the pathological examination of the lymph nodes guides is of critical importance in the decision process regarding the use of postoperative adjuvant therapy. However, lymph node axillary dissection can be followed by significant locoregional morbidity. The sentinel lymph node (SLN) technique was developed as a means of avoiding the full exploration of the axilla and consists in the identification of the first lymph node in the lymphatic drainage system of the breast tumour in the homolateral axilla. It has been demonstrated that the status of the SLN is highly predictive for the presence or absence of tumour involvement in the remaining lymph nodes in the axilla. In this study we evaluated the SLN technique using both 99mTc labelled dextran 500 and patent blue V dye in relation to the classical lymph node resection a series of 56 women with early breast cancer who attended the Breast Unit of the Academic Hospital of the Federal University of Rio Grande do Sul, Brazil. To our knowledge this is the first report in the literature of the utilization of 99mTc dextran 500 for the SLN technique. As there are no similar commercially available dedicated radiopharmaceuticals labelled for use in lymphoscintigraphy studies, we report on an effective method to label dextran 500 with 99mTc which proved to be simple, inexpensive and yielded similar results for SLN identification compared with those given in the literature. The median age of the patients was 57 years (range 32-82 years). Seventeen patients were age 50 years or less, and 39 patients were older than 50 years. The median tumour size was 2.0 cm (range 0.8-7.0 cm). The mapping of the SLN was possible in all cases during the transoperative period by using a hand-guided gamma probe and a blue dye. A median of 2.0 (range 1-5) SLN were excised per patient. The median of axillary lymph nodes excised per patient was 21 (range 10-36). The calculated sensitivity and specificity of the method were 95.6% and 100%, respectively. The negative predictive value and overall accuracy were 97% and 98.2%, respectively. In conclusion, the SLN technique was feasible and produced similar positive results as previously reported in the literature.

Adult↗
PubMed2001

Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines.

In the present study, we examined the relationship between cell phenotype and cell survival of three human non-small cell lung carcinoma cell lines (A549, NCI-H596 and NCI-H520). Cells in exponential growth at various densities were incubated for 24 h at 37 degrees C in a 5% CO2 humidified atmosphere and then exposed to UV radiation for 1 min (256 nm, 40 W, source-to-target distance 100 cm). After two days the surviving cells were quantified by sulforhodamine beta staining and DNA fragmentation assay. The differences in UV sensitivity at 60 x 10(3) cells/cm2 among the cell lines were not related to the proliferative state of the cells but to the extent of intercellular contact. In contrast to A549 and NCI-H596, irradiated NCI-H520 cells presented lower DNA fragmentation and an aggregated cell culture phenotype even prior to confluence, suggesting that a contact-effect mechanism provides further protection against UV radiation.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer.

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

Antimetabolites, Antineoplastic↗
PubMed2001

von Willebrand factor antigen levels in plasma of patients with malignant breast disease.

von Willebrand factor (vWF) is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag) by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 +/- 78 U/dl in patients with cancer, 148.4 +/- 59 U/dl in patients with benign disease and 130.6 +/- 45 U/dl in controls (P<0.005). We also detected a significant increase in the levels of vWF:Ag (P<0.0001) in patients with advanced stages of the disease (stage IV = 263.3 +/- 113 U/dl, stage IIIB = 194.0 +/- 44 U/dl) as compared to those with earlier stages of the disease (stage I = 155.3 +/- 65 U/dl, stage IIA = 146.9 +/- 75 U/dl). In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression.

Adolescent↗
PubMed2000

A phase I trial of cisplatin plus decitabine, a new DNA-hypomethylating agent, in patients with advanced solid tumors and a follow-up early phase II evaluation in patients with inoperable non-small cell lung cancer.

The authors describe a phase I trial of cisplatin plus decitabine, a novel DNA-hypomethylating agent, in patients with advanced solid tumors, which was followed by an early phase II evaluation of the combination in patients with inoperable non-small cell lung cancer (NSCLC). In the phase I trial, cisplatin was studied at a fixed dose of 33 mg/m2, while decitabine was escalated in four (I-IV) dose escalation levels (45, 67, 90 to 120 mg/m2, respectively) in consecutive groups of at least 3 patients per dose level. Decytabine was administered to the patients as a two-hour intravenous infusion, while cisplatin was given intravenously immediately after the end of decitabine infusion. Both agents were given on days 1-3 every 21 days. Twenty-one patients were included in the phase I trial. Dose level IV (120 mg/m2 decitabine) was considered the maximum tolerated dose (MTD), while the dose-limiting toxicities were neutropenia, thrombocytopenia and mucositis. The recommended doses for phase II trials in good- and poor-risk patients were 90 (level III) and 67 mg/m2 (level II), respectively. One short-lasting partial response was observed in a patient with cervical cancer, while two minor regression were documented in a patients with NSCLC and cervical cancer, respectively. Dose level II was selected for the phase II trial in patients with inoperable NSCLC. Fourteen consecutive patients were included in this part of the study. The median age of the patients was 57 years (range, 39-75), male/female ratio of 11/3 and a median WHO performance status 1 (0-2). The stage of disease were IIIB (5) and IV (9). Prior irradiation to the chest was given in one case. A total of 30 treatment courses were evaluable for toxicity and response, with a median of 2 courses per patient (1-4). Grade 3-4 neutropenia and thrombocytopenia were observed in about half of the cases. Mucositis, diarrhea, nausea and vomiting, and skin rash were also observed in some patients. Three minor responses were documented, which lasted for 4, 16 and 36 weeks. Median survival of patients was 15 weeks (4-38). In conclusion, the cisplatin plus decitabine combination did not exhibit significant antitumor activity in patients with NSCLC at the dose and schedule applied in this trial to justify its further evaluation in this patient population.

Adult↗
PubMed2000

Anti-cancer drug discovery and development in Brazil: targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds.

Throughout medical history, plant products have been shown to be valuable sources of novel anti-cancer drugs. Examples are the VINCA: alkaloids, the taxanes, and the camptothecins, derived from the Madagscan periwinkle plant Catharantus roseus, the Pacific yew Taxus brevifolia, and the Chinese tree Camptotheca acuminata, respectively. For this reason, the South-American Office for Anti-Cancer Drug Development has implemented a large-scale project of acquisition and testing of compounds isolated from South American medicinal plants. The species are selected on the basis of a potentially useful phytochemical composition by consulting ethnopharmacological, chemosystemic, and ecological information. The collected samples are dried and first extracted with an organic solvent, then with distilled water. These crude extracts are evaluated at a concentration of 50 microg/ml for antiproliferative activity against one cell line. Extracts that significantly inhibit the growth of the cells (>/=50%) at relatively low concentrations (</=50 microg/ml) are submitted to the more comprehensive disease-oriented screen of the U.S. National Cancer Institute. In parallel, these samples are further purified by bioassay-guided purification, involving repeated fractionation by diverse chromatography methods. If the active substance is expected to represent a novel structure, it is identified by appropriate chemical techniques, mechanistic studies are performed with a wide diversity of tumor models and laboratory techniques, and efforts are undertaken for the synthesis of potentially more useful analogs.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Phenotype modulation of cellular UV-sensitivity.

Mammalian cell shape is critically important to cell differentiation, apoptosis, cell division, and growth arrest. In the present study we examined the relationship among cell density, cell phenotype (which include shape and coupling) and cell survival using the human A549, H596 and H520 non-small cell lung carcinoma lines. Thus, cells from monolayers, aggregated and suspended cultures at different densities were exposed to UV-radiation and both the density and the phenotype of the cells induce shifts in cellular growth rate. Except in suspended cultures, we observed a UV-sensitivity closely related to the proliferative status of the cells. The variability of the cellular response to UV were investigated taking into account the shape and the coupling potential of the cell lines, suggesting that an intercellular-contact mechanism provides further protection against UV-radiation damage.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Tamoxifen inhibits particulate-associated protein kinase C activity, and sensitises cultured human glioblastoma cells not to etoposide but to gamma-radiation and BCNU.

We investigated the potential mechanisms of tamoxifen cytotoxicity in the U-373, U-138, and U-87 human glioblastoma cell lines, namely interference with protein kinase C (PKC) activity, the oestrogen receptor, and/or the production of transforming growth factor beta 1 (TGF-beta 1). We further examined the effects of tamoxifen on the cytotoxicity exerted by gamma-radiation, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and etoposide in this cell line panel. Thus, the cells were treated for 4 days with tamoxifen, gamma-radiation, purified recombinant human TGF-beta 1 (rhTGF-beta 1), BCNU, or etoposide, either alone or at certain combinations. Cellular responses were evaluated with the sulphorhodamine B assay, as well as by multiple drug effect analysis, and related to PKC activities in particulate and cellular fractions; cellular oestrogen receptor contents; and the influence of rhTGF-beta 1 on cell growth. Tamoxifen inhibited cell proliferation as well as the phosphorylation capacity of the particulate, but not of the cytosolic fractions dose-dependently, at comparable kinetics, and at IC50 values of approximately 15 microM. At these concentrations, tamoxifen acted synergistically with gamma-radiation (4- to 6-fold) and additively with BCNU (approximately 2-fold), but did not affect etoposide cytotoxicity. The cells were negative to immunostaining for the oestrogen receptor, and rhRGF-beta 1 did not influence their growth up to 100 nm. Our data suggest that tamoxifen can sensitise cultured glioblastoma cells not to etoposide but to gamma-radiation and BCNU, possibly through interference with membrane PKC, supporting its evaluation in experimental protocols for primary malignant gliomas.

Antineoplastic Agents↗
PubMed1999

Sequence-dependent growth inhibition and DNA damage formation by the irinotecan-5-fluorouracil combination in human colon carcinoma cell lines.

We evaluated irinotecan (CPT-11) together with 5-fluorouracil (5-FU) for improved cell growth inhibition with respect to that by either agent alone in the human colon carcinoma cell lines SW620, HT-29 and SNU-C4. Cells were exposed for 24 h to each drug, as well as to various combinations and sequences of low, fixed doses of one drug with higher varying doses of the other, cultured for two more days in drug-free medium and then assessed for growth response with the sulphorhodamine B assay. Multiple drug effect analysis was used to evaluate the data, which were then related to the amount of DNA damage occurring in the cells which was determined by a fluorescence-enhancement assay for DNA unwinding. Cellular responses were also related to thymidylate synthase topoisomerase I and carboxyl esterase activities, which were assessed by a ligand-binding and a 3H-release assay; a DNA decatenation assay; and a spectrophotometric method, respectively. IC50 values for 5-FU alone in the SW620, HT29 and SNU-C4 cells were 15.3 +/- 0.8, 8.2 +/- 1.3 and 2.2 +/- 0.7 microM, respectively, and for CPT-11 2.0 +/- 0.9, 2.5 +/- 0.5 and 3.8 +/- 0.3 microM, respectively. The differential responses to 5-FU alone were possibly determined by differences in substrate affinity and conversion rate of thymidylate synthase (K(m) of approximately 7.5, 5.0 and 2.5 microM and V0 of approximately 800, 200 and 2400 microM/h, respectively). The comparable cellular responses to CPT-11 alone might be accounted for by the counterbalancing effects of differences in topoisomerase I (1, 1, and 1.5 arbitrary units, respectively) and carboxyl esterase activities (5055 +/- 1789, 4080 +/- 752, 1713 +/- 522 mU/mg, respectively). IC20 CPT-11 prior to 5-FU was additive to synergistic in SW620, HT-29 and SNU-C4 cells (CIs of 0.7 +/- 0.1). By contrast, pre-treatment with IC20 5-FU antagonised the CPT-11-mediated growth inhibition (CIs of 1.9 +/- 0.4, 1.7 +/- 1.1, 2.5 +/- 0.9, respectively). Simultaneous drug treatment did not produce more cell growth inhibition than either drug alone in the SW620 and the HT-29 cells, but was additive or antagonistic in the SNU-C4 cells (CIs of 1.1 +/- 0.3 and 2.2 +/- 1.4), depending on the ratio of the drugs. Increased DNA damage in the SW620 and HT-29 cells was only seen when IC20 CPT-11 preceded IC50 5-FU, resulting in approximately 40 and 25%, respectively, more lesions than for IC50 5-FU alone. In the SNU-C4 cells, not only such a treatment, but also simultaneous drug treatment produced (30 to 60%) more DNA damage than either drug alone. Our results show clear sequence-dependent antiproliferative effects and DNA damage formation by CPT-11 and 5-FU at combinations of low, fixed doses with higher, varying doses in cultured human colon carcinoma cells, and may be of relevance to the design of improved chemotherapeutic regimens in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Essential drugs for cancer therapy: a World Health Organization consultation.

The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.

Antineoplastic Agents↗
PubMed1998

Gemcitabine and paclitaxel combinations in non-small cell lung cancer.

Gemcitabine and paclitaxel are new cytotoxic agents that have been used both as single agents and in combination, particularly with cisplatin, in the therapy of non-small cell lung cancer (NSCLC) with promising results. The lack of overlapping toxicities and different mechanisms of action of gemcitabine and paclitaxel make the combination of these drugs appealing in the treatment of NSCLC. A number of phase I and II trials are evaluating the use of this combination of cytotoxic agents as first-line therapy and as second-line therapy in patients with advanced NSCLC. In ongoing phase II trials using a 21-day schedule, the combination of gemcitabine and paclitaxel therapy appears to be well-tolerated, with response rates ranging from 29% to 58% and hematologic toxicities that are mild to moderate in severity. Other reported toxicities included alopecia, fatigue, and flu-like symptoms, which were also mild to moderate. However, grade 2/3 neurotoxicity was also reported. In conclusion, preliminary results from these early phase II trials of gemcitabine/paclitaxel combination therapy in advanced NSCLC are encouraging.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Phase II trial of paclitaxel and ifosfamide as a salvage treatment in metastatic breast cancer.

PURPOSE: Treatment results in patients failing first-line chemotherapy in metastatic breast cancer (MBC) are still unsatisfactory, with patients exhibiting poor responses to salvage therapy and a short overall survival. Both paclitaxel and ifosfamide are able to produce objective tumor responses in this disease. Therefore, the antitumor effects and toxicity of their combined use could be worthwhile studying in patients progressing after doxorubicin-containing combinations. PATIENTS AND METHODS: This Phase II trial of paclitaxel/ifosfamide included patients with bi-dimensionally measurable metastatic breast cancer in second or third relapse, following anthracycline-containing regimens; ECOG PS < 2, and adequate hepatic, cardiac, renal, and hematological functions. Paclitaxel 175 mg/m2 was given on day 1, in a 3-hour infusion with appropriate antiallergic pre-medication; while ifosfamide 1.8 g/m2 was given on days 2, 3, 4 with mesna 360 mg/m2 i.v., 15 minutes before and 4 hours after ifosfamide administration, and 720 mg/m2 P.O. 8 hours later at home, also on days 2, 3, 4. The cycles were repeated every 21 days, on an outpatient basis. RESULTS: Twenty-four patients were accrued for the study and 23 were considered eligible for the evaluation of toxicity and response. Previous chemotherapy included: CMF/FAC (16 cases); CMF plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C (2 cases): and FAC/mitomycin C, vinblastine, and etoposide (5 cases). There were 11 (48%) objective responses (95% C.I.:27-69%), including 2 (9%) CR and 9 (39%) PR (95% C.I.:0-21% and 19-61%, respectively). Five (22%) patients attained disease stabilization. Median response duration was 7+ months (range 4 to 20+), and the median overall survival was 12 months (range 4-23+). The regimen was well tolerated. WHO nausea/ vomiting grades 1-2, alopecia grade 3, and neutropenia grades 1-2 were seen in most patients. Four patients experienced mild neuropathy, while it was grade 3 in 1 case. Seven patients had grade 3 neutropenia. In addition, grade 4 neutropenia associated with fever was documented in other 4 cases. No hypersensitivity reactions were seen. One case of reversible tachycardia after drug administration was seen. Myalgia grades 1-2 was also reported in some patients. CONCLUSION: These results suggest that the present regimen has significant activity in heavily pretreated patients with a MBC, with a manageable toxicity profile. Further trials exploiting the above mentioned drug combination are warranted.

Adult↗
PubMed1997

Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.

PURPOSE: In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy. PATIENTS AND METHODS: Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard. RESULTS: The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing. CONCLUSION: At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.

Acquired Immunodeficiency Syndrome↗