PubMed Health⌕ Search

Biomedical subjects

W C Mertens

Publications and source records attributed to W C Mertens.

At least 19 recordsLinked to original sources
PubMed1998

Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials.

Ocular melanoma is an uncommon malignancy that, in the presence of metastatic disease, has a poor prognosis for response to treatment and survival. Patients with ocular melanoma are often excluded from clinical trials because of the impression that these patients have a poorer response rate to treatment with anticancer agents and poorer survival, possibly related to the predominance of the liver as a site of metastasis. Sixty-four eligible patients with advanced melanoma arising from ocular primary tumors were entered into seven phase II clinical trials of anticancer therapy activated by the Southwest Oncology Group (SWOG) during the 1980s. Eligible patients with nonocular primaries entered into these trials (420 patients) served as a comparison group for survival, pretreatment characteristics, and response rates. Multivariate Cox model analysis of survival data (with survival from the time of study registration as the primary end-point) was conducted. Among the 484 patients observed, patients with ocular melanoma were older than those with nonocular primary tumors and were more likely to have visceral metastasis, metastasis to the liver, and only one metastatic site at registration, primarily to viscera and liver. The median overall survival after registration to study for both groups was 5 months. There was no significant difference in overall survival between patients with ocular melanoma and those with nonocular melanoma after adjusting for a number of prognostic factor (p = 0.43). Furthermore, the overall objective response rate of patients with ocular melanoma in these studies was not significantly different from that achieved in the nonocular group (9% vs. 11%; p = 1.00). Patients with advanced ocular or nonocular melanoma have similar response rates and survival in this series of cooperative group phase II trials. Patients with ocular primaries should not be excluded from investigational studies in advanced melanoma.

Antineoplastic Agents↗
PubMed1997

Osteosarcoma and other tumors of bone.

The report of results from a major randomized clinical trial of neoadjuvant chemotherapy for operable osteosarcoma and the experience of two groups with neoadjuvant chemotherapy for patients with malignant fibrous histiocytoma of bone mark the major clinical advances of the past year. Further work on prognostic factors, including p-glycoprotein, oncogenes, and genes related to cell cycle control, as well as promising novel therapeutics, appeared in the literature and will likely result in new areas of clinical investigation.

Bone Neoplasms↗
PubMed1996

Oral indomethacin and ranitidine in advanced melanoma: a phase II study.

As a result of preclinical data demonstrating the antitumour and antimetastatic efficiency of indomethacin in murine models, and the clinical observation of occasional tumour regression in patients with advanced melanoma treated with indomethacin together with ranitidine, a Phase II study was performed of prolonged administration of these two oral agents in combination. Seventeen patients were entered into the study and commenced on indomethacin 50 mg three times daily; the dose was escalated to a maximum of 75 mg three times daily in patients who tolerated the starting dose. Ranitidine was administered concurrently at a dose of 150 mg twice daily. One patient with uveal melanoma metastatic to the liver achieved a partial response, with slow shrinkage of a biopsy-proved liver metastasis (objective response rate 6 percent; 95 percent CI0-29). Another patient demonstrated a minor response in pelvic lymph nodes. The combination of indomethacin and ranitidine has negligible activity in advanced malignant melanoma; a response may require months to be achieved.

Administration, Oral↗
PubMed1996

Osteosarcoma and other tumors of bone.

Steady progress in the delineation of prognostic factors and the identification of genetic alterations and of potential mechanisms of oncogenesis mark the contributions to the literature on osteosarcoma for the past year. A new cytokine and chemotherapy combination has shown promise, and additional work on chemotherapy regimens containing ifosfamide will undoubtedly stimulate interest in a new generation of randomized clinical trials that will be essential for further refinement of therapy for osteosarcoma.

Bone Neoplasms↗
PubMed1995

High-dose continuous venous infusion of interleukin-2: influence of dose and infusion rate on tumoricidal function and lymphocyte subsets.

Previous clinical studies have demonstrated a dose-response relationship between enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials with low dosages of the cytokine. This has not been demonstrated for high-dose (greater than 18 x 10(6) IU/m2 per day) IL-2. We completed phase II trials of sustained administration of indomethacin and ranitidine with IL-2 given as a continuous infusion over 5 days for three courses. Peripheral blood mononuclear cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were tested for tumoricidal function against K562 and Daudi targets; these results were then correlated with actual delivered dose and mean infusion rate per course. Similar correlations were calculated between delivered dose or infusion rate and absolute and proportional counts of lymphocyte subsets as determined by flow cytometry. No enhancement of in vitro tumoricidal function with either increasing delivered dose or increasing infusion rate was seen. No consistent pattern of correlation was found between the absolute counts of lymphocyte subsets after each course of IL-2 with delivered dose or infusion rate. The percent rise in absolute counts of selected T- and NK-cell subsets at the end of course 1 compared with baseline values correlated positively with infusion rate; however, a similar correlated between the infusion rate and an increase in lymphocyte tumoricidal function was lacking. Little evidence was found for improved tumoricidal function of mononuclear cells or consistent enhancement of lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18 x 10(6) IU/m2 per day in a 5-day continuous infusion schedule.

Carcinoma, Renal Cell↗
PubMed1995

Osteosarcoma and other tumors of bone.

Although no major advances in local or systemic therapy have been reported, further progress has been made in the identification of genetic alterations and prognostic factors in primary as well as recurrent osteosarcoma. Further reports on the use of a variety of imaging techniques in the quantification of tumor response to neoadjuvant chemotherapy have also appeared. Publications describing high-dose methotrexate pharmacokinetics, the impact of this therapy on patient outcome, and a report of a pilot study evaluating the feasibility of higher dose intensity cisplatin and doxorubicin may lead to new and important randomized clinical trials in the future.

Antineoplastic Agents↗
PubMed1995

Adjuvant chemotherapy for soft tissue sarcomas.

Despite considerable interest in this subject and the completion of a number of randomized trials, the use of adjuvant chemotherapy after definitive local treatment for patients with soft tissue sarcomas remains problematic. This article reviews randomized clinical trials completed and published to date, and explores new strategies for future studies.

Antineoplastic Agents↗
PubMed1994

Docetaxel in advanced renal carcinoma. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Most patients diagnosed with renal carcinoma developed metastatic disease at some time during their course, with available therapy inducing response in only a small proportion of patients. Docetaxel (Taxotere, RP56976) a semi-synthetic analogue of paclitaxel with a broad range of in vitro antitumor activity, was evaluated in a phase II study. METHODS: Eligibility criteria included histologically proven metastatic or advanced, bidimensionally measurable disease, no prior chemotherapy, immunotherapy, or hormonal therapy, adequate hematologic (neutrophils > or = 2.0 x 10(9)/L, platelets > or = 100 x 10(9)/L) and biochemical (serum creatinine and bilirubin < or = 1.5 x normal, transaminases < or = 3 x normal) parameters, WHO performance status of at least 2, and a life expectancy of > 12 weeks. Docetaxel was administered in a dose of 100 mg/m2 as a 1 hour intravenous infusion every 3 weeks. The first 2 patients entered onto the study were not premedicated for hypersensitivity reactions; subsequent patients received dexamethasone 10 mg and diphenhydramine 50 mg i.v. 30 minutes prior to docetaxel. RESULTS: Twenty patients were entered onto the study, with 2 considered inevaluable for response. Sixty cycles of therapy were administered, with only 2 cycles delivered at a dose of 55 mg/m2 or less. No objective responses were seen; 1 patient demonstrated a mixed response. Neutropenia was significant, with 42/60 cycles developing grade 3/4 granulocytopenia. Fifty-five percent of patients demonstrated hypersensitivity reactions despite the premedication regimen employed, higher than that of the phase I studies which established the dose and schedule used in this trial. CONCLUSIONS: 1) Docetaxel is an ineffective agent in advanced renal carcinoma. 2) The high rate of hypersensitivity reactions suggests the need for more intensive premedication and/or slower infusion times at this dose level.

Adult↗
PubMed1994

Osteosarcoma and other tumors of bone.

Steady progress has been made in the identification of genetic alterations and prognostic factors in osteosarcoma. Imaging studies continue to be employed not only for preoperative staging, but to quantify factors such as tumor bulk and tumor response to neoadjuvant chemotherapy. Although there have been no major refinements of local or systemic therapy, continuing research into novel agents (eg, liposomal muramyl, tripeptide phosphatidylethanolamine, and antisense oligonucleotides to insulin-like growth factor receptors) hold promise for new therapies for this disease in the future.

Adolescent↗
PubMed1994

Utility of 111In-labelled leukocytes in patients completing high-dose interleukin-2 therapy: a pilot study.

Interleukin-2 (IL-2) therapy has resulted in modest response rates in patients with renal carcinoma and melanoma, but few reproducible pre- or post-treatment parameters have been associated with response, and tumour localization with lymphokine-activated killer cells has only occasionally been demonstrated. Eight patients (seven with renal carcinoma and one with melanoma) treated on a protocol with chronic indomethacin and ranitidine with three courses of continuous infusion of IL-2 had peripheral blood leukocytes withdrawn 12-36 h after completion of IL-2 therapy, labelled with 111In tropolone and reinjected. Images were taken at 4 and 20 h after reinjection. Three of these patients achieved objective responses to therapy, but none demonstrated uptake of radioisotope-labelled leukocytes in known tumour-bearing areas. Two nonresponding patients (one renal carcinoma, one melanoma) demonstrated uptake in all known tumour areas; one further nonresponding patient demonstrated uptake in the region of a femoral metastasis, but not in other bulky areas of disease. No correlation between scan uptake, and leukocyte subsets could be demonstrated. Although occasional patients demonstrate tumoural accumulations of 111In-labelled leukocytes after completion of therapy with IL-2, this does not appear to be associated with response.

Carcinoma, Renal Cell↗
PubMed1994

Glutathione S-transferase expression in renal cell carcinoma: a new marker of differentiation.

Expression of two GST isoenzymes (alpha and pi) was assessed immunohistochemically in 46 cases of renal cell carcinoma (RCC) for which clinical follow-up was available. In the normal kidney GST alpha stained most intensely in the proximal convoluted tubules and GST pi in distal tubules/collecting ducts. All 46 tumors studied stained positively for GST alpha with most demonstrating strong cytoplasmic and nuclear reactivity. GST pi immunostaining was positive in 35/46 cases (76%). Five-year survival for patients with GST pi positive tumors was 88% versus 50% for those with GST pi negative tumors (P < 0.008). Loss of GST mRNA has been reported in RCC and it has been suggested that this may represent a dedifferentiation program in RCC. These data support this hypothesis and further indicate a potential value for GST pi as a prognostic indicator in RCC.

Adult↗
PubMed1993

Sustained indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced malignant melanoma: a phase II study.

Experimental work has shown that, during the development of tumours, host macrophages are triggered to produce high levels of prostaglandin E2 which inactivates natural killer cells and suppresses lymphokine activated killer cell development. Sustained, uninterrupted indomethacin treatment, when combined with interleukin-2 (IL-2), can totally eradicate experimental metastases. Most trials utilizing high dose IL-2 employ indomethacin and ranitidine in order to alleviate or prevent IL-2 toxicity, but only administer these medications concurrently with IL-2 therapy. A Phase II trial was conducted in patients with advanced melanoma. Patients received 50-75 mg indomethacin three times daily and 150 mg ranitidine twice daily, starting at least 1 week prior to IL-2 and continuing until intolerance or disease progression. Continuous venous infusion IL-2 was administered for three courses, each consisting of 5 days of treatment at 18 x 10(6) iu/m2/day for the first course with escalation of dose for the subsequent courses if toxicity allowed. Twenty-one patients were eligible to receive all components of therapy. Three patients achieved an objective response (one complete and two partial), giving a response rate of 14%. However, two of these objective responses (one complete and one partial) were achieved on indomethacin and ranitidine alone, prior to the commencement of IL-2 therapy. In this study, indomethacin and ranitidine, without IL-2, have been shown to have antitumour activity in advanced melanoma; continuous infusion IL-2 appeared to add little to the response seen with these two agents.

Adult↗
PubMed1993

Malignant paraganglioma with skeletal metastases and spinal cord compression: response and palliation with chemotherapy.

Paragangliomas (carotid body tumours, chemodectomas) may arise in any area of the body where sympathetic ganglia are present, including chemoreceptors, the adrenal medulla and retroperitoneal ganglia. Increasing numbers of patients are being reported with vertebral metastases and spinal cord compression for which either decompression laminectomy or external beam radiotherapy, or both, are required. Patients with vertebral metastases may develop progression of disease after radiation therapy. There is little published information on the use of chemotherapy in this clinical situation. We report a case of metastatic paraganglioma complicated by spinal cord compression showing evidence of clinical benefit from chemotherapy after progressive disease and symptoms developed in a region previously treated by radiation therapy.

Adult↗
PubMed1993

Sustained oral indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced renal cell carcinoma.

Experimental work in murine models has shown that, during the development of tumors, prostaglandin E2 produced by host macrophages inactivates natural killer cells and suppresses lymphokine-activated killer (LAK) cell development. Chronic indomethacin therapy when combined with interleukin-2 (IL-2) can totally eradicate experimental lung metastases in these models. A phase II trial was performed to study the clinical efficacy of chronic indomethacin and intermittent IL-2 therapy in patients with advanced renal cell carcinoma. Patients were placed on indomethacin and ranitidine orally at least one week prior to commencing therapy with IL-2. IL-2 was given by continuous infusion for three courses, each consisting of 5 days of treatment with 6 days of rest. Initial dose of IL-2 was 18.0 x 10(6) IU/m2/day for the first course with escalation to 27.0 x 10(6) IU/m2/day for the second and 36.0 x 10(6) IU/m2/day for the third course, if toxicity allowed. Patients were admitted to a general oncology ward for therapy with IL-2, and vasopressor agents were not used. Thirty-two patients were eligible, with 7 patients withdrawing early from the study. Twenty-five patients went on to receive at least one course of IL-2. Two complete and three partial responses were seen for an objective response rate of 5/25 (20%) for eligible and treated patients or 5/32 (16%) for all patients entered onto the study, regardless of treatment status. The response rate to this regimen is comparable with other high dose IL-2 regimens in renal cell carcinoma, including those employing adoptive therapy with lymphokine-activated killer cells.

Carcinoma, Renal Cell↗
PubMed1993

Gemcitabine in advanced renal cell carcinoma. A phase II study of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) an anticancer agent with activity in preclinical models, was felt to be a promising new chemotherapy drug which warranted testing in patients with advanced renal cell carcinoma. METHODS: Eighteen patients with histologically proven metastatic or locally recurrent renal cell carcinoma and bidimensionally measurable disease were accrued to a phase II study of gemcitabine administered intravenously on days 1, 8 and 15 of a 28 day treatment cycle. Initial doses of gemcitabine were 800 mg/m2; doses in subsequent cycles were escalated to a maximum of 1250 mg/m2, toxicity permitting. RESULTS: One partial response was seen for a response rate of 6%. Hematologic toxicity was not severe with this dosing schedule; however, two patients developed dyspnea with bronchospasm after repeated injections of drug. CONCLUSIONS: The dose and schedule of gemcitabine employed results in only a modest response rate in patients with advanced renal carcinoma. Investigators should be aware of the possibility of dyspnea and bronchospasm developing shortly after gemcitabine administration.

Adult↗
PubMed1993

Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship?

Reports published in the English literature of clinical trials utilizing intravenous strontium 89 (89Sr) in the treatment of patients with prostatic adenocarcinoma metastatic to bone were reviewed. Correlation coefficients were calculated for increasing dose of 89Sr and complete pain relief and complete and partial pain relief. Statistically significant positive correlations were obtained for complete relief of pain. Positive correlations were also found between those patients who had at least partial pain relief (defined as at least a 50% reduction in analgesia requirement), but these did not reach significance. This analysis suggests that a dose response relationship may exist between the dosage of 89Sr administered, and complete relief of pain due to skeletal metastases. The optimal dosage of 89Sr in this clinical situation has not been established, and prospective, carefully executed and analyzed randomized trials will be required to test whether and to what extent dose intensity of 89Sr determines outcome independently of other factors.

Adenocarcinoma↗