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Biomedical subjects

D L Lamm

Publications and source records attributed to D L Lamm.

At least 73 records · Page 4Linked to original sources
PubMed1992

Optimal BCG treatment of superficial bladder cancer as defined by American trials.

Immunotherapy provides an effective alternative approach to chemotherapy in the management of superficial bladder cancer. The first widely used immunotherapy, bacillus Calmette-Guérin (BCG), eradicates residual tumour bacillus Calmette-Guérin (BCG), eradicates residual tumour in one half of patients with carcinoma in situ. Unlike chemotherapy, induction of immunity against transitional cell carcinoma has the potential of protecting patients from tumours which have not yet developed. Controlled trials suggest that BCG immunotherapy reduces disease progression, decreases the need for cystectomy and prolongs survival. While the optimal BCG treatment schedule remains unknown and may in fact vary from one patient to another, data clearly suggest that a single 6-week induction course is suboptimal. In 150 randomized patients with CIS treated with 120 mg Connaught BCG, Southwest Oncology Group (SWOG) investigators found that just 3 additional weekly treatments at week 12 increased complete response from 70 to 82% (p less than 0.05). Intravesical BCG is clearly superior to oral BCG, and controlled studies have demonstrated that percutaneous administration is not necessary. While evidence suggests that BCG is the best available treatment for superficial bladder cancer and 95% of patients have no significant toxicity, serious and even fatal toxicity can occur. Sepsis can occur with intravenous absorption and often appears to result from hypersensitivity. Limited clinical and animal model experience suggests that cycloserine improves survival over treatment with isoniazid and rifampicin, but optimal treatment of BCG sepsis is isoniazid 300 mg, rifampicin 600 mg, and prednisolone 40 mg daily.

Administration, Intravesical↗
PubMed1992

Carcinoma in situ.

Carcinoma in situ is a high-grade and aggressive manifestation of transitional-cell carcinoma of the bladder that has a highly variable course. The treatment of CIS has undergone dramatic changes since this malignancy was first recognized. While cystectomy was once recommended as the initial treatment of choice, recognition of the highly variable prognosis and the uniformly high response rate to intravesical BCG has prompted a more conservative approach to management. While it is recommended that patients be offered the option of radical cystectomy, data do not currently exist to confirm that cystectomy provides a superior survival or quality of life compared with an initial trial of BCG immunotherapy followed by salvage cystectomy if needed. With current optimal BCG immunotherapy regimens, which consist of a 6-week course of BCG followed by three weekly instillations at 3 months, 6 months, and every 6 months for 3 years, the complete response rate is 82%; and it is estimated that more than 75% of patients having a complete response will remain continuously disease free for 5 or more years. Patients who fail BCG immunotherapy without evidence of progression may yet be candidates for intravesical chemotherapy, photodynamic therapy, or alternative immunotherapies such as alpha-2b interferon, bropirimine, or keyhole limpet hemocyanin.

Administration, Intravesical↗
PubMed1992

Complications of bacillus Calmette-Guérin immunotherapy.

Knowing when to give and when to withhold BCG will prevent most complications, but even when all precautions are taken, some complications will occur. The initial step in the treatment of infectious complications is the use of isoniazid. Routine prophylactic isoniazid should not be given, as animal studies have confirmed that immune stimulation, and presumably antitumor activity, can be inhibited by isoniazid prophylaxis. However, when cystitis persists more than 2 days or is so severe that it does not respond to symptomatic treatment, isoniazid 300 mg daily is used to control the symptoms, prevent progressive infection, and avoid the overgrowth of BCG, which can result in excessive organisms and suppression of the immune response. If symptoms progress despite isoniazid treatment or do not begin to abate within 1 to 2 weeks, rifampicin 600 mg daily is added. Rifampicin is given from the beginning in patients with potentially severe extravesical BCG infection such as pneumonitis, hepatitis, or nephritis. In patients with symptoms such as fever, malaise, or bladder irritation that respond within a few days, it generally is necessary to continue antitubercular antibiotics for only 2 weeks. Those with extravesical infection and those who do not respond promptly to treatment are treated for 3 months, and those with severe or deep-seated infection are treated for 6 months. The current recommendation for the treatment of sepsis after BCG administration, based on limited clinical experience and controlled animal experimentation, is to use isoniazid and rifampicin plus prednisolone 40 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1992

Long-term results of intravesical therapy for superficial bladder cancer.

Intravesical chemotherapy will cause complete regression of existing papillary tumor in one third to one half of patients. Controlled clinical trials have demonstrated that chemotherapy reduces the short-term incidence of tumor recurrence by 15% to 18%, but by 5 years, the number of patients suffering tumor recurrence is equal to that in patients treated with surgery alone. Tumor progression cannot occur in the absence of tumor recurrence, but existing studies of intravesical chemotherapy have failed to demonstrate significant reduction in disease progression or mortality rate with treatment. Immunotherapy has the advantage of a mechanism of action different from that of cytotoxic chemotherapy. Immunotherapy with BCG has resulted in complete tumor regression in one half or more of treated patients with papillary tumors and in more than 70% of those with CIS. Controlled studies similarly demonstrate a significant reduction in tumor recurrence, and protection from tumor recurrence has been observed to persist for 5 years or more. At the present time, data remain limited, but three controlled studies have found statistically significant reductions in the rate of disease progression, and one has found a significant reduction in the mortality rate, with BCG immunotherapy. These observations provide convincing evidence that immunotherapy is the treatment of choice for patients with aggressive superficial tumors and suggest that the development of immunotherapeutic alternatives to BCG is likely to be rewarding.

Administration, Intravesical↗
PubMed1991

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.

BACKGROUND: In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question. METHODS: Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS: For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS: As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

Administration, Cutaneous↗
PubMed1991

Treatment of murine transitional cell carcinoma with intralesional interleukin 2 and murine interferon gamma.

The antitumor effect of intralesionally administered recombinant interleukin-2, alone or in combination with recombinant interferon gamma was studied in murine transitional cell carcinoma, MBT2. In the initial prophylactic model treatment was started at day one at the site of tumor inoculation. Maximal and significant reduction in tumor volume occurred in groups receiving 4,000 units of recombinant interleukin 2 and 10(7) colony forming units Bacillus Calmette Guerin (p less than 0.00001 vs saline control). In the same experiment, a reduction in tumor incidence and increase in survival occurred in groups receiving 4,000 units of recombinant interleukin 2, 1,000 units of recombinant interleukin 2 plus 2,000 units of recombinant interferon gamma, as well as 10(7) colony forming units Bacillus Calmette Guerin relative to saline control (p less than 0.005). The dose-response effect of recombinant interleukin 2 alone was also tested in a model of an established transitional cell carcinoma. Intralesional injection treatments were initiated after tumors were palpable. Reduction in tumor volume was observed in the group receiving 8,000 units of recombinant interleukin 2 (p = 0.01 vs saline control), but no significant advantage in survival was noted.

Animals↗
PubMed1991

Immunotherapy of murine bladder cancer by irradiated tumor vaccine.

This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

Animals↗
PubMed1991

Prospective randomized comparison of intravesical with percutaneous bacillus Calmette-Guerin versus intravesical bacillus Calmette-Guerin in superficial bladder cancer.

Conflicting reports of the necessity for percutaneous bacillus Calmette-Guerin (BCG) administration with intravesical BCG prompted us to evaluate its benefit in a randomized prospective comparison of intravesical versus intravesical with percutaneous BCG therapy. Intravesical Tice BCG was given in a dose of 50 mg. with or without percutaneous BCG weekly for 6 weeks, at 8, 10 and 12 weeks, at 6 months and every 6 months thereafter. Tumor recurrence was documented in 13 of 30 patients (43%) receiving only intravesical BCG and in 15 of 36 patients (42%) receiving intravesical plus percutaneous BCG. The addition of percutaneous BCG to intravesical therapy did not increase treatment efficacy in this study.

Administration, Intravesical↗
PubMed1991

IL-2/LAK cell treatment for advanced cancers with emphasis on a novel administration.

Interleukin-2 (IL-2) is a substance produced by activated blood cells called helper T-lymphocytes and has been shown to stimulate the body's immune system. IL-2 may cause certain tumors to regress when administered intravenously to laboratory animals and humans. Lymphokine activated killer (LAK) cells are white blood cells that have been stimulated with IL-2 in vitro. LAK cells are capable of killing tumor cells both in vitro and in vivo, especially when given along with IL-2. Although this form of treatment has been found to be effective in patients with certain cancers who no longer benefit from standard forms of therapy, the anti-cancer effects of IL-2/LAK cell treatment are limited by the serious, life-threatening side effects of high-dose intravenous administration, and by the high cost. A treatment program with low-dose, intralymphatically-administered LAK/IL-2 in patients with advanced cancer is a promising alternative which circumvents these major problems and concerns, while maintaining high response rates.

Blood Component Transfusion↗
PubMed1990

Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma.

To assess the value of autolymphocyte therapy (ALT) in the treatment of metastatic renal-cell carcinoma, 90 patients were randomised to receive every month for six months oral cimetidine plus an infusion of autologous peripheral blood lymphocytes activated in vitro by a previously generated autologous lymphokine mixture, or cimetidine alone. The median follow-up was 15 months. Survival time for the autolymphocyte group was approximately 2.5 times that for the cimetidine group (p = 0.008). Patients who had greater than 500 pg interleukin-1 (IL-1) per ml autologous lymphokine mixture had a six-fold survival advantage over those with less than 500 pg/ml (p less than 0.00005). Men treated with ALT had a four-fold survival advantage (p = 0.001) over men who received cimetidine only. Infusion of the cultured autolymphocytes was accompanied by mild, self-limited fever in 11 of the 45 ALT patients, and by only one instance in which fever was accompanied by tachypnoea and hypotension.

Actuarial Analysis↗
PubMed1990

A randomized prospective comparison of oral versus intravesical and percutaneous bacillus Calmette-Guerin for superficial bladder cancer.

Reports of a dramatic decrease in tumor recurrence and regression of muscle invasive disease with oral bacillus Calmette-Guerin prompted us to conduct a randomized prospective comparison of oral bacillus Calmette-Guerin with the standard intravesical plus percutaneous therapy. Oral therapy consisted of 200 mg. Tice bacillus Calmette-Guerin 3 times each week. Intravesical and percutaneous Tice bacillus Calmette-Guerin at a dose of 50 mg. was given weekly for 6 weeks, at 8, 10 and 12 weeks, then at 6 months and every 6 months thereafter. Minimal side effects confirmed the safety of oral bacillus Calmette-Guerin. Tumor recurrence was documented in 21 of 33 oral bacillus Calmette-Guerin patients (64%) and 18 of 55 (33%) who received intravesical plus percutaneous therapy (p less than 0.002, chi-square test). We were unable to demonstrate any antitumor activity of oral bacillus Calmette-Guerin in this study.

Administration, Intravesical↗
PubMed1990

The preparation, handling and use of intravesical bacillus Calmette-Guerin for the management of stage Ta, T1, carcinoma in situ and transitional cell cancer.

The increasing use of bacillus Calmette-Guerin in the treatment of patients with low stage bladder cancer will inevitably bring attention to problems of proper use and toxicity. There is a need to identify patients who are most likely to benefit from this therapy and those who may be at risk for serious complications.

Administration, Intravesical↗
PubMed1990

Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.

Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. Complications from bacillus Calmette-Guerin therapy are usually minor but serious and even fatal reactions can occur. Five recent cases illustrate the gravity of bacillus Calmette-Guerin sepsis. One man with severe debility and the organic brain syndrome died acutely with a fever of 40 C. Two men had frank sepsis that progressed to multiorgan failure and death. Sepsis progressed despite the use of isoniazid, rifampin and streptomycin. Two men who had equally progressive sepsis with intravesical bacillus Calmette-Guerin survived with the use of cycloserine for the first 72 hours of treatment. Triple antituberculous antibiotics, including cycloserine, may be lifesaving. Sepsis resulted from intravenous absorption through inflamed or disrupted urothelium. Bacillus Calmette-Guerin treatment should not be administered in the presence of severe cystitis or after grossly traumatic catheterization.

Administration, Intravesical↗
PubMed1989

Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer.

Between January 1978 and February 1984, 120 patients with superficial bladder tumors and/or carcinoma in situ were enrolled in previously reported therapeutic trials of bacillus Calmette-Guerin. Of all treated patients 78 per cent responded to initial therapy, with a followup of 13 to 120 months (median 67 months). Of the 18 patients who failed 10 were treated with repeat, intensified courses. Nine patients who had recurrent tumors within 3 to 30 months after initiation of bacillus Calmette-Guerin therapy (median 6 months) eventually ceased having recurrence. Status free of disease in the 9 patients ranged from 25 to 90 months since the last recurrence (median 64 months). With retreatment of some of the early failures, the initial success rate of 78 per cent was increased to 89 per cent. These data support the concept that intravesical immunotherapy with bacillus Calmette-Guerin should be repeated in patients who initially appear not to respond. The data also suggest that bacillus Calmette-Guerin induces a durable beneficial response rather than simply delays eventual tumor recurrence.

Administration, Intravesical↗