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D L Lamm

Publications and source records attributed to D L Lamm.

At least 37 records · Page 2Linked to original sources
PubMed1997

Allium sativum (garlic) treatment for murine transitional cell carcinoma.

BACKGROUND: Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. METHODS: C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. RESULTS: In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). CONCLUSIONS: The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.

Adjuvants, Immunologic↗
PubMed1997

Improved detection of recurrent bladder cancer using the Bard BTA stat Test.

OBJECTIVES: To evaluate the BTA stat Test in the detection of recurrent bladder cancer. METHODS: Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. RESULTS: The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. CONCLUSIONS: The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.

Aged↗
PubMed1997

Treatment of renal cell carcinoma with 5-fluorouracil and alfa-interferon.

OBJECTIVES: Renal cell carcinoma is relatively resistant to both chemotherapy and immunotherapy. Response, survival, duration of response, and toxicity of treatment were evaluated in patients with advanced renal cell carcinoma receiving a continuous intravenous infusion of 5-fluorouracil (5-FU) and low dose subcutaneous alfa-2b-interferon. METHODS: Between 1989 and 1994, 21 patients with advanced renal cell carcinoma underwent treatment with continuous intravenous infusion of 5-FU, 200 mg/m2/day, and subcutaneous injections of recombinant interferon alfa-2b (IFN-alpha), 1 x 10(6) U/day. RESULTS: Objective response was observed in 9 patients (43%). Complete response occurred in 4 patients (19%): 2 with lung, 1 with bone, and 1 with liver metastasis. Partial response occurred in 5 patients (24%). Three of 4 complete responders remain alive without recurrence. Mean survival rate was 195 weeks among complete responders, 184 weeks among partial responders, and 88 weeks among nonresponders. The overall mean duration of response was 101 weeks. Responders developed progression of disease a mean of 62 weeks after the initial response to therapy. Mild dose-dependent toxicity was related to 5-FU infusion. Nearly all toxicities subsided with the temporary cessation of 5-FU infusion and/or decreasing the dose of the infusion. Few if any of the toxicities appear to be directly related to the low dose interferon injections. CONCLUSIONS: Although this study is based on a small sample size, we believe that the encouraging complete and partial responses, apparent prolongation of survival, and manageable toxicity of this combination therapy warrant further investigation with larger randomized trials.

Adult↗
PubMed1997

A multicenter trial evaluation of the fibrin/fibrinogen degradation products test for detection and monitoring of bladder cancer.

PURPOSE: Presently there is a lack of effective, noninvasive tests for the detection and monitoring of bladder cancer. Measurement of fibrin/fibrinogen degradation products in urine has been shown to be a useful indicator of bladder carcinoma. The objective of this study was to evaluate the AuraTek FDP rapid immunoassay device for the detection of urinary fibrin/ fibrinogen degradation products associated with bladder cancer. MATERIALS AND METHODS: A prospective multicenter study was conducted to compare AuraTek FDP with urinary cytology and hemoglobin dipstick for the detection of bladder cancer in 192 patients with a history of bladder cancer. RESULTS: AuraTek FDP was significantly more sensitive (68%) than conventional urinary cytology (34%, p < 0.001) or hemoglobin dipstick (41%, p < 0.001) in the detection of bladder tumors, particularly for low stage low grade disease. In subjects with invasive disease (T2-T4) the AuraTek FDP test had a sensitivity of 100%. Specificity of AuraTek FDP was 96% for healthy subjects, 86% in patients with urological disease other than bladder cancer and 80% for patients under surveillance for bladder cancer but with a negative cystoscopic finding at the time of assay. CONCLUSIONS: This simple, rapid (less than 7 minutes) point of care test is superior to conventional urine cytology and hemoglobin dipstick as an aid in the detection of bladder cancer.

Aged↗
PubMed1996

Bropirimine immunotherapy of upper urinary tract carcinoma in situ.

OBJECTIVES: Bropirimine has been shown to be effective in treating approximately 50% of patients with carcinoma in situ (CIS) of the bladder in recent clinical trials. Patients with upper tract CIS were treated with bropirimine to determine whether this oral drug might be effective in that setting. METHODS: Twenty-four patients with negative radiographic findings and positive cytologic evidence for upper tract CIS in one or both ureters received bropirimine (3.0 g/day orally) for 3 consecutive days each week for up to 1 year. Ureteral collection of urine or barbotage for cytologic analysis was performed quarterly thereafter. RESULTS: Ten (48%) of 21 evaluable patients had a negative ureteral cytologic analysis after 12 weeks (5 patients) or 24 weeks (5 patients). Of these 10 patients, 8 continue to have negative cytology for a period of 3 to 30 months (median, more than 9 months). In 2 patients, negative cytology reverted to positive at 6 and 9 months, respectively, during therapy. Twelve (50%) of the 24 patients reported no toxicity. Three patients stopped treatment at 2, 3, and 3 weeks due to pruritic rash, nausea and vomiting, and severe bone pain, respectively. Therapy was stopped in 1 additional patient between 4 and 5 months because of transient liver enzyme elevations, yet this patient has had a continuous negative cytologic analysis for more than 9 months. CONCLUSIONS: Orally administered bropirimine may be effective therapy for CIS of the ureter or renal pelvis, with acceptable toxicity in most patients. Further efforts to better define this activity as well as the possible need for maintenance or intermittent long-term therapy are warranted.

Adjuvants, Immunologic↗
PubMed1996

Oral bropirimine immunotherapy of carcinoma in situ of the bladder: results of a phase II trial.

OBJECTIVES: Bropirimine is an orally administered immunostimulant that has been shown to have activity against carcinoma in situ (CIS) of the bladder. To further assess this potential activity, bropirimine was administered to 42 patients for bladder CIS in a Phase II trial. METHODS: Patients were treated with bropirimine 3.0 g/day by mouth for 3 consecutive days each week up to 1 year. Cystoscopy with biopsies and bladder wash cytology were performed quarterly. RESULTS: Twenty (61%) of 33 evaluable patients converted malignant biopsies and bladder wash cytology to negative, including 6 (50%) of 12 who failed prior bacillus Calmette-Guérin (BCG) immunotherapy, 14 (67%) of 21 who had not received prior BCG therapy, and 12 (80%) of 15 with primary CIS. Median response duration exceeds 21 months. Four of the 20 responders did have a papillary tumor recurrence at 3 to 15 months, all Stage Ta or T1. Mild toxicity (grade I or II) suggestive to interferon induction or administration occurred in one third of patients. Headache, transient hepatic enzyme elevations, skin rash, and arthralgias each occurred in 5% to 14% of the patients, with nausea or emesis in 21%. Grade 1 tachycardia/palpitations or chest pain each were noted in 5%. CONCLUSIONS: Oral bropirimine can induce remission of bladder CIS with acceptable toxicity at 3.0 g/day. Bropirimine may be a valuable alternative to cystectomy for some failures of BCG therapy and may have the potential to replace BCG as front-line therapy because of its ease of administration.

Adjuvants, Immunologic↗
PubMed1996

Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment.

PURPOSE: We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS: A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS: Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS: NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Biomarkers, Tumor↗
PubMed1996

Local toxicity patterns associated with intravesical bacillus Calmette-Guérin: a Southwest Oncology Group Study.

BACKGROUND: While the efficacy of bacillus Calmette-Guérin (BCG) immunotherapy has been demonstrated, the relative benefit, given a seemingly high incidence and severity of toxicities, remains an issue. Adequate understanding and management of toxicities can maximize the safety of the treatment and enable the administration of required doses of BCG intravesical therapy. METHODS: All week-to-week symptoms recorded for the 143 immunotherapy-naive participants assigned to the BCG arm of SWOG-8216, BCG vs. Doxorubicin in Superficial Bladder Cancer were analyzed in order to document the pattern of toxicities in the first six week induction course of intravesical BCG treatments. The statistical analysis consisted of fitting logistic regression models to these data for the probability of irritative bladder symptoms (IBS). RESULTS: In the optimal model, the probability of IBS depends only on whether there was IBS associated with the previous treatment, and not on which treatment. The estimated probability of having IBS when there were no IBS associated with the previous instillation is 0.136, whereas the estimated probability of having IBS when there was IBS associated with the previous instillation is 0.689. CONCLUSIONS: Irritative bladder symptoms are unlikely in the week after the first intravesical BCG treatment. Once a patient experiences IBS, he or she is more likely to have IBS with the next and subsequent treatments. Clinicians can use the findings of this analysis when informing their patients about the treatment course and when making decisions about continuing treatments.

Administration, Intravesical↗
PubMed1996

Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract.

PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.

Aged↗
PubMed1996

Therapy of superficial bladder cancer.

Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (Ie, Ta, Tl, and carcinoma in situ [CIS]) with specific objectives that include treating existing/residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival irrespective of the treatment. Intravesical chemotherapy has shown a decrease in short-term tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Presently, bacillus Calmette-Guèrin vaccine (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcome on tumor recurrence rate, disease progression, and prolongation of survival. Prostatic urethral mucosal involvement with bladder cancer can also be effectively treated with BCG intravesical immunotherapy. Interferons, keyhole limpet hemocyanin and photofrin-photodynamic therapy are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in intravesical therapy and prophylaxis of superficial TCC.

BCG Vaccine↗
PubMed1995

Drug therapy of bacillus Calmette-Guérin sepsis.

Intravesical bacillus Calmette-Guérin (BCG) is widely used for the treatment of transitional cell carcinoma of the bladder. Although it is usually well tolerated, sepsis can occur, which has resulted in at least eight deaths [3]. The survival of Connaught BCG-infected mice treated with single and combination antibiotic and steroid therapy was evaluated. Triple-drug therapy with isoniazid, rifampin, and prednisolone resulted in 53% survival compared with 25% survival in the control group (P = 0.0209). A survival of only 10.5% was observed with treatment using prednisolone alone. This survival was worse than that of the control group (25%), and approached statistical significance (P = 0.0669). Our data suggest that BCG sepsis probably has components of both a hypersensitivity reaction and bacterial sepsis; they support the current use of combination antibiotic and steroid therapy for treatment of BCG sepsis in humans, but argue against treatment with steroids alone.

Animals↗
PubMed1995

BCG in perspective: advances in the treatment of superficial bladder cancer.

The management of superficial bladder cancer has advanced significantly in recent years. Controlled clinical trials suggest the benefits of cytotoxic chemotherapy apply primarily to well-differentiated tumours, are short-term and do not include a reduction in disease progression. In contrast, intravesical bacillus Calmette-Guérin (BCG) immunotherapy is effective in high-grade tumours, provides long-term protection from tumour recurrence and reduces disease progression. Controlled clinical trials have consistently demonstrated that BCG provides superior protection from tumour recurrence compared with thiotepa or doxorubicin. In comparisons with mitomycin C, only two of six studies found a significant advantage for BCG therapy; both studies evaluating high-risk patients showed a significant reduction in tumour recurrence with BCG compared with mitomycin C. Controlled trials have demonstrated that newer chemotherapies and more intensive regimens are not superior to standard thiotepa treatment. However, controlled comparisons of immunotherapy suggest that BCG is superior to both interferon and keyhole-limpet haemocyanin. Comparative studies showing BCG to be superior to chemotherapy and other immunotherapies have employed what we now know to be suboptimal BCG regimens. Using three additional weekly BCG (Connaught) treatments at 3 months, complete response in carcinoma in situ is increased from 73 to 87%. In patients who are disease free, maintenance BCG using three weekly treatments at 6-month intervals improves long-term disease-free status in stage Ta and T1 bladder cancer from 50 to 83%. Such maintenance therapy improves the excellent 86% survival obtained with a single 6-week course of BCG to 92% (p < 0.04).

Administration, Intravesical↗
PubMed1995

Apparent failure of current intravesical chemotherapy prophylaxis to influence the long-term course of superficial transitional cell carcinoma of the bladder.

During the 4 decades since the first introduction of intravesical chemotherapy, 3,899 patients were enrolled in 22 randomized prospective controlled studies. Of these 22 studies 13 reported a statistically significant benefit of intravesical chemotherapy. With varying followup, the reported decrease in the incidence of patients with tumor recurrence averaged only 14% (range -3 to +43%). Unfortunately, long-term (5-year) studies show no decrease in the incidence of recurrent tumor. Maintenance chemotherapy has failed to improve these results and data suggest that a single early postoperative instillation may, in fact, be most effective. Among 10 studies that include progression data none showed decreased tumor progression, and overall among 2,011 randomized patients progression occurred in 7.5% of those receiving intravesical chemotherapy and 6.9% of those treated by surgery alone. Since intravesical chemotherapy has been demonstrated in animal models to be carcinogenic, these data raise the concern that intravesical chemotherapy might possibly be carcinogenic in humans. In the absence of demonstrated long-term benefit we question the advisability of routine prophylactic intravesical chemotherapy.

Administration, Intravesical↗