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R M Bukowski

Publications and source records attributed to R M Bukowski.

At least 55 records · Page 3Linked to original sources
PubMed1997

Recent advances in diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract.

Neuroendocrine tumors of the gastrointestinal tract are rare tumors that can be classified as APU-Domas (amine precursor uptake and decarboxylation). They can be subdivided into the carcinoid tumors of the gastrointestinal submucosa and the islet cell endocrine tumors of the pancreas. Although the majority of tumors that become clinically apparent are malignant, they are frequently slow growing. Despite this, neuroendocrine tumors may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better radiographic imaging and more accurate localization techniques. Medical therapies with somatostatin analogues, omeprazole, and locoregional tumor ablation have made a positive impact on curative and palliative therapy. This review updates the recent efforts made in the radiographic imaging and therapeutics of the gastrointestinal neuroendocrine tumors.

Adenoma, Islet Cell↗
PubMed1997

Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response.

A phase II trial was conducted in patients with metastatic renal cell carcinoma, to assess the clinical efficacy and immunoregulatory effects of continuous-infusion recombinant interleukin-2 (rIL-2) (9.0 x 10(6) IU/m2/day on days 1-5, 8-12, 15-19, and 22-26) and subcutaneously administered recombinant human interferon-alpha 2b (rHuIFN alpha 2b) (10.0 x 10(6) U/m2/day TIW). Thirty-six patients with metastatic renal cell carcinoma, performance status of 0-1, and measurable disease who had not received prior rIL-2, rHuIFN alpha 2b, or chemotherapy were treated. Patients with CNS metastases, active infections, history of another malignancy within 3 years, and those requiring corticosteroids were ineligible. Cycles of rIL-2 and rHuIFN alpha 2b were administered in the outpatient department every 6-8 weeks in stable or responding patients until patient tolerance or a complete response were reached. Doses were modified for grade III or IV toxicity. Ancillary studies included three-color immunocytometric analysis of peripheral blood lymphocytes, repetitive tumor biopsies for immunohistologic analysis of infiltrating cells and proliferative responses of tumor infiltrating lymphocytes, and preliminary studies of changes in peripheral blood T-lymphocyte signal transduction molecules [T-cell receptor (TCR)-zeta, p56ick, p59fyn]. Thirty-six eligible patients were treated, with 6 of 36 patients (17%, 95% confidence interval 6-33%) responding (3 complete response, 3 partial response). In two of the partial responders, and in an additional three patients with either minimal tumor regression (one patient) or stable disease (two patients), surgical removal of residual disease was undertaken. The median survival of all patients was 14 months. The toxicity of this regimen was severe, but outpatient administration was possible in most instances. Immunoregulatory effects on T-cell subsets included increases in various CD3+ CD25+/- HLADr+/- subsets unrelated to response. Tumor biopsies before and/or during therapy were obtained in 17 patients, and no consistent alterations in the degree of T-lymphocyte or macrophage infiltrates could be detected. In a subset of patients, tumor infiltrating lymphocyte proliferative responses and levels of peripheral blood T-cell signal transduction molecules (TCR-zeta, p56lck, p59fyn) were investigated. Abnormalities were found in selected patients, which improved during rIL-2/rHuIFN alpha 2b therapy. This cytokine combination produces tumor regression in selected patients with metastatic renal cell carcinoma. Surrogate immunologic markers associated with response were not identified; however, preliminary studies demonstrate investigation of immune defects and their reversal with cytokine therapy is possible.

Adult↗
PubMed1997

Defective granzyme B gene expression and lytic response in T lymphocytes infiltrating human renal cell carcinoma.

Granzyme B is a protein thought to play a pivotal role in the cytolytic functions of T cells. In view of this, the inducibility of this gene in freshly isolated T cells (T-TILs) infiltrating human renal cell carcinoma (RCC) in vitro was examined by using the reverse transcriptase-polymerase chain reaction (RT-PCR). A reduction in granzyme B messenger RNA (mRNA) expression in stimulated T-TILs from five of nine patients with RCC compared with autologous peripheral blood T cells was noted. The reduced expression was observed after multiple stimuli including anti-CD3 antibody, interleukin-2 (IL-2), and phytohemagglutinin (PHA). Because CD8+ T cells represent the predominant cytotoxic population, the ability of this cell population to express granzyme B mRNA after stimulation also was examined. When compared with CD8+ peripheral blood lymphocytes (T-PBLs) from patients with RCC and normal donors, the induction of granzyme B mRNA was reduced in CD8+ T-TILs. CD8+ T-TILs also had lower non-major histocompatibility complex (MHC)-restricted cytotoxic activity than did CD8+ T-PBLs against both Daudi cells and allogeneic RCC cell lines. These results show that in a subset of patients with RCC, depressed lytic activity of CD8+ TILs compared with CD8+ PBLs is present. Reduced granzyme B mRNA expression also was noted in selected patients.

Carcinoma, Renal Cell↗
PubMed1997

Clinical practice guidelines: renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common renal malignancy and is increasing at an annual rate of approximately 2% worldwide. Metastatic RCC is among the more chemotherapy-refractory malignancies, with a 5-year survival rate less than 2%. A variety of therapies are currently under investigation for the treatment of metastatic RCC, particularly involving immunotherapeutic agents such as interferon alfa. OBJECTIVES: To review and compare historical and current data that define practice guidelines in the treatment of RCC. DISCUSSION: Of the various treatment modalities available for RCC, only surgery with complete removal of tumor burden can be considered as potentially curative, since the tumor is resistant to chemotherapy, hormonal therapy, and radiation therapy. However, biologic response modifiers (BRMs)-particularly immunotherapeutic agents such as interferon alfa-have been extensively studied and appear to produce objective tumor regression in selected patients with advanced disease. CONCLUSIONS: In patients with metastatic RCC, performance status is the most important predictor of outcome, and should therefore be utilized for therapeutic decision making. Immunotherapy with BRMs such as recombinant interferon alfa and recombinant interleukin-2 has been associated with meaningful antitumor responses in selected patients. Combination therapy with recombinant interferon alfa, recombinant interleukin-2, and 5-fluorouracil may offer considerable promise, and the subcutaneous administration of recombinant interferon alfa and recombinant interleukin-2 may improve the tolerability and convenience of these cancer treatments by reducing side effects and permitting outpatient administration. As treatment expectations for metastatic RCC are limited, experimental approaches are warranted.

Carcinoma, Renal Cell↗
PubMed1996

Phase II trial of subcutaneously administered granulocyte-macrophage colony-stimulating factor in patients with metastatic renal cell carcinoma.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is involved in the differentiation and proliferation of various hematopoietic precursors. It also has been reported to enhance the antitumor activity of various mature effector cells. Previous reports have noted preclinical antitumor activity in a murine model utilizing genetically engineered tumor cells and instances of tumor regression in patients with solid tumors receiving GM-CSF. In the present study, a Phase II trial of human recombinant GM-CSF (GM-CSFrh) in patients with metastatic renal cell carcinoma (RCC) was conducted to investigate further the potential antitumor activity of this cytokine. METHODS: Twenty-six eligible patients with metastatic RCC received 3 microgram/kg of GM-CSFrh subcutaneously for 14 days, with cycles repeated every 28 days. RESULTS: Two of 26 patients (8%; 95% confidence interval 1-25%) demonstrated partial tumor responses during GM-CSFrh therapy. Both individuals who responded had received prior therapy. A median of three cycles per patient were administered, and toxicity was mild. CONCLUSIONS: GM-CSFrh may mediate tumor regression in patients with metastatic RCC; however, the level of activity in previously treated patients is low.

Adult↗
PubMed1996

Cytokine and chemokine expression in tumors of mice receiving systemic therapy with IL-12.

The cellular and molecular mechanisms of IL-12-mediated anti-tumor activity have been examined. BALB/c mice bearing established s.c. RENCA or CT26 tumors that were treated daily with IL-12 showed essentially complete tumor regression while tumors in untreated animals grew progressively. Examination of inflammatory gene expression in tumor tissue from treated vs untreated mice revealed the selective expression of IFN-gamma and the IFN-gamma-inducible CXC chemokine IP-10. Immunohistologic analysis demonstrated that tumors from treated mice were heavily infiltrated with CD8+ T cells and Mac-1+ mononuclear cells. Tumor regression in IL-12-treated mice was associated with expression of the lytic effector molecules perforin and granzyme B. These findings support the hypothesis that the anti-tumor function of IL-12 treatment depends upon the induced expression of IFN-gamma by T cells and/or NK cells, the amplification of the immune response mediated by IFN-gamma-induced expression of chemoattractant cytokines, and the IL-12-dependent potentiation of the cytolytic effector function of recruited CD8+ T cells.

Adenocarcinoma↗
PubMed1996

Clinical effects of amifostine (Ethyol) in patients treated with carboplatin.

Amifostine is a compound that has been developed as a radio- and chemoprotectant. It is a prodrug, giving rise to the active thiol, WR-1065. Amifostine has been demonstrated to reduce the toxicity of ionising radiation, alkylating agents and platinum compounds. Preclinical studies have shown that amifostine can reduce the myelosuppression of carboplatin in a murine model tumour system without reducing the efficacy of therapy. In fact, in this model system, the antitumour effects of carboplatin against the OVCAR-3 cell line were actually greater with than without amifostine. Based on these preclinical studies, clinical trials of the combination of carboplatin and amifostine have been undertaken. A phase I trial of carboplatin and amifostine in pretreated patients demonstrated that two doses of amifostine 740 mg/m2/dose may be safely administered with carboplatin. The maximum tolerated dose (MTD) of carboplatin that could be administered with amifostine was 500 mg/m2, suggesting the hypothesis that amifostine increases the MTD of carboplatin from 400 to 500 mg/m2. To test this hypothesis, a randomised trial of carboplatin 500 mg/m2 versus carboplatin 500 mg/m2 plus two doses of amifostine 910 mg/m2/dose has been performed. Analysis of this trial is not complete, but initial results suggest a reduction of first-cycle thrombocytopenia, from a median platelet nadir value of 85 x 10(9) cells/l for carboplatin alone to 144 x 10(9) cells/l for the combination of carboplatin plus amifostine. Similarly, the median first-cycle granulocyte nadir was 1.6 x 10(9) cells/l without amifostine but 2.4 x 10(9) cells/l with the cytoprotectant. Neither of these first-cycle differences was statistically significant, but these effects are being maintained with repeated dosing, so that an increase in delivered cumulative carboplatin dose seems possible with the use of amifostine. These promising data indicate that continued studies of amifostine with carboplatin are justified and that the effects of amifostine on the thrombocytopenia produced by carboplatin-containing combination chemotherapy regimens should be investigated.

Amifostine↗
PubMed1996

Amifostine (Ethyol): dosing, administration and patient management guidelines.

Cytoprotection utilising amifostine (Ethyol, WR-2721) is an evolving strategy to protect normal cells from the toxicity of chemotherapy. The dosing and administration guidelines are reviewed. The recommended dose of amifostine is 910 mg/m2 as a 15-min infusion prior to chemotherapy. Toxicity of this agent is moderate with hypotension and nausea/vomiting being observed in variable numbers of patients. Administration of amifostine with chemotherapy is simple and is associated with acceptable toxicity.

Amifostine↗
PubMed1996

The need for cytoprotection.

The toxicity associated with chemotherapy is significant and dose limiting. Multiple organ systems can be affected, with both acute and chronic side effects producing adverse effects. The concept of cytoprotection, or the selective protection of normal tissues is a strategy now being investigated in preclinical and clinical models. Systemic approaches have included the use of compounds such as sodium thiosulphate, diethyldithiocarbamate and amifostine. The most promising results have been obtained with the organic thiophosphate compound amifostine (Ethyol, WR-2721).

Amifostine↗
PubMed1996

HIV infection among Brazilian transvestites in a prison population.

Eighty-two male transvestites imprisoned in Casa de Detenção (São Paulo, Brazil) were tested for HIV antibodies, and completed a questionnaire investigating their demographics, arrest and imprisonment records, sexual practices, and drug use. Data were then analyzed to evaluate the incidence of HIV infection and its association with various behavioral and other factors. Sixty-four of 82 (78%, 95% confidence interval [CI], 67-87%) transvestites were positive for HIV infection. The factors associated with significant differences in positivity among these individuals were the time spent in prison and the number of sexual partners during the previous year. It appears that the high rate of infection in this group obscured the importance of other risk factors and behavioral patterns potentially associated with infection. Given the social environment and the high rate of HIV infection among imprisoned transvestites, their role as "vectors" for dissemination of HIV in urban areas of Brazil may be significant.

Adult↗
PubMed1996

Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with malignancy.

A phase I trial of simultaneously administered recombinant interleukin-2 (rIL-2) and recombinant human IL-4 (rHuIL-4) was conducted to evaluate the toxicity and the clinical and immunologic effects of this cytokine combination. Thirty-nine eligible patients with refractory malignancy were treated at eight different dose levels (1A to 3B): 1-3 of rIL-2 [3.0, 12.0, and 48.0 x 10(6) IU/m(2) i.v. three times weekly (TIW)] and A-C of rHuIL-4 (40, 120, and 400 mu g/m(2) s.c. TIW). The toxicity of these two cytokines was moderate and was comparable with that seen with rIL-2 alone. The maximal tolerated dose (MTD) of the combination was not reached because of lack of sufficient rHuIL-4 but is at least 48.0 x 10(6) IU/m(2) of rIL-2 and 120 mu g/m(2) of rHuIL-4. Two patients with melanoma had partial responses. The immunologic effects included increases in absolute lymphocyte numbers, and the CD3- /CD56+/ CD2+, total CD56+, CD8+, and CD16c+ lymphocyte subsets with increasing rIL-2 dose levels, but not with rHuIL-4. This increase in natural killer (NK) cells in the peripheral blood was accompanied by an increase over baseline in NK lytic activity against K562 targets; however, concomitant increases in lymphokine-activated killer (LAK) activity (Daudi targets) were not seen. The CD3+, CD4+, and CD3+/CD25+/HLA-Dr+ T-cell subsets also increased, and these increases were related to both increasing rIL-2 and rRuIL-4 doses. Finally, in four of six patients, serial tumor biopsies demonstrated increases in major histocompatibility complex (MHC) class I or II antigen expression on tumor cells or increasing T-cell infiltrates during cytokine therapy or both. This trial demonstrated that rIL-2 and rHuIL-4 can be administered simultaneously with acceptable toxicity. The immunologic findings demonstrated the expected rIL-2-associated increases of CD56+ and CD16c+ lymphocytes and NK activity, and interestingly, no development of LAK activity. These findings suggest regulatory effects of rHuIL-4 on rIL-2-related effects in vivo.

Adjuvants, Immunologic↗
PubMed1996

Resistance to interleukin 6 in human non-small cell lung carcinoma cell lines: role of receptor components.

The role of interleukin 6 (IL-6) in regulating the growth of three human non-small cell lung carcinoma (NSCLC) cell lines (NSCLC-3, NSCLC-5, and NSCLC-7, derived from a primary lesion, a brain lesion, and lymph node metastases, respectively) was examined. Although IL-6 alone did not alter the growth of these cells, the addition of soluble IL-6 receptor (sIL-6R) led to the inhibition of proliferation of one of the NSCLC cell lines, NSCLC-5. This antiproliferative effect was neutralized by antibodies to IL-6 and the IL-6R binding and signaling component (gp130). The IL-6-related cytokines, leukemia inhibitory factor and oncostatin M, inhibited proliferation of NSCLC-5 cells but were ineffective in NSCLC-3 and NSCLC-7 cells. NSCLC-7 cells (but not NSCLC-3 or NSCLC-5 cells) secreted biologically active IL-6 and expressed IL-6R. However, antibodies to IL-6 or gp130 failed to alter the proliferation of NSCLC-7 cells. All three cell lines expressed gp130 mRNA and protein. The level of expression of gp130 protein varied in the three cell lines (NSCLC-7 > NSCLC-3 > NSCLC-5). The examination of tyrosine phosphorylation of gp130 (as an early event in IL-6 signal transduction) revealed that gp130 could be phosphorylated in all cell lines after stimulation with IL-6 and/or IL-6 + sIL-6R. These results demonstrate that the mechanisms responsible for IL-6 resistance in different NSCLC cell lines vary and involve defects at either one or more levels of the IL-6 signaling cascade. In the NSCLC-5 cell line, IL-6 resistance (which can be reversed in the presence of sIL-6R) is due to the transcriptional inactivation of the IL-6R gene. In contrast, in the other two cell lines (NSCLC-3 and NSCLC-7), defect(s) in the signaling cascade downstream of gp130 phosphorylation, together with a lack of expression of IL-6R in NSCLC-3 cells, result in IL-6 resistance.

Antigens, CD↗
PubMed1996

Phase I trial of subcutaneous interleukin 3 in patients with refractory malignancy: hematological, immunological, and pharmacodynamic findings.

We conducted a Phase I trial of s.c. recombinant human interleukin 3 (rhIL-3) to evaluate the toxicity, maximal tolerated dose, pharmacokinetics, and in vivo biological effects of this cytokine. Thirty-one patients with refractory cancer were entered into the study between November 1991 and June 1993. Therapy consisted of s.c. rhIL-3 daily for 15 days administered to cohorts of three to nine patients at dose levels of 60-4000 microgram/m2/day. Cycles were repeated at intervals of 28 days. Seventy-five cycles of rhIL-3 were administered (median, two per patient) and the maximal tolerated dose was 2000 microgram/m2/day. Toxicity was moderate, with most patients developing chills, fever, and myalgia. Dose-limiting toxicity consisted of diarrhea (two patients) and headache (one patient). Hematological effects of rhIL-3 included significant dose-related increases of WBC (P < 0.001), neutrophils (P < 0.001), and eosinophils (P < 0.001). Platelet counts and absolute lymphocyte numbers also increased. Various CD3(+) lymphocyte subsets increased; however, lytic activity (natural killer and lymphokine-activated killer) of peripheral blood lymphocytes was not enhanced. Serum levels of the soluble IL-2 receptor increased in a dose-related fashion, and IL-2-induced lymphocyte proliferation also was increased variably. Pharmacokinetic studies were performed in 13 patients, and area under the curve and maximal concentration values increased with increasing rhIL-3 dose levels (P < 0.001) and correlated with maximal changes from baseline in WBC, neutrophils, and eosinophils. rhIL-3 antibodies were detected in 8% of patients by day 29 of cycle 1 but were not neutralizing. rhIL-3 is well tolerated when administered s.c. and has reproducible hematological and immunological effects. The pleiotropic effects of this cytokine on various in vivo biological parameters were demonstrated clearly. Further studies of its immunoregulatory effects are warranted.

Adult↗
PubMed1995

Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor-infiltrating lymphocytes.

The progression of tumors such as renal cell carcinoma (RCC), despite the presence of substantial lymphocytic infiltrates (TIL), suggests that the ability of the local immune response to control tumor growth is impaired. Cytokine gene expression was examined to further investigate the nature of this response. Initial studies were performed with frozen tumors using PCR-assisted mRNA amplification with cytokine-specific primers for interleukin 10 (IL-10), interleukin 2 (IL-2) and interferon-gamma (IFN-gamma). IL-2 mRNA was not detected, despite the presence of T cells as defined by the expression of CD3 gamma mRNA. In contrast, mRNA for IFN-gamma was expressed in 4/9 and for IL-10 in 5/9 tumors. To confirm this, 5 fresh tumor specimens were examined, and PCR demonstrated that IL-10 mRNA was detectable in 4/5 tumors from which RNA was isolated at the time of nephrectomy. In these experiments multiple cycles and dilutions were employed to semi-quantitate the expression of IL-10. To identify potential sources of this cytokine in the tumor bed, IL-10 mRNA expression in freshly isolated lymphocytes and tumor cells, TIL lines, cultured RCC and established RCC lines was examined. Our studies demonstrate that within the tumor TIL may be one source of IL-10. Lymphocyte-enriched populations from 4/5 tumors expressed IL-10 mRNA as did 4/6 freshly isolated tumor cell preparations. IL-10 gene expression was not detected, however, in tumor cells after one passage in vitro in short-term cultured RCC tumor cells (passages 2-5) or in established RCC tumor cell lines. Finally, 4/9 CD4+ and 2/5 CD8+ TIL lines expressed IL-10 mRNA either constitutively or after stimulation with anti-CD3 antibody. This finding was associated with IL-10 production in vitro. Our studies demonstrate that IL-10 mRNA is frequently present in RCC tumors and may originate from the tumor-infiltrating mononuclear cell population.

Base Sequence↗
PubMed1995

Expression of blood group antigen A by stage I non-small cell lung carcinomas.

To clarify the significance of blood group antigen A (BAA) expression by neoplastic cells, we studied patients who had curative resections of stage I non-small cell lung carcinomas. Immunohistochemical staining using monoclonal antibodies was used to detect BAA expression by paraffin-embedded carcinoma cells. One hundred three patients were studied; mean age was 62.6 years, and 70 (68%) were male. Histologic types were as follows: adenocarcinoma, 52 (50.5%); squamous cell, 25 (24.3%); large cell, 24 (23.3%); and adenosquamous, 2 (1.9%). Histologic grades were as follows: I, 13 (12.6%); II, 26 (25.3%); and III, 64 (62.1%). All patients had American Joint Committee on Cancer stage I tumors: 65 patients (63.1%) had T1 tumors, and 38 (36.9%) had T2 tumors. Recurrences developed in 25 (24.3%) and metachronous malignancies in 4 (3.9%). Survival was 75% +/- 4.8% at 3 years and 66.6% +/- 7.5% at 5 years. Eighty-nine patients (86.4%) were blood group A and 14 (13.6%) were AB. Ninety-five (92.2%) were secretors of BAA and 8 (7.8%) were not. The expression of BAA by neoplastic cells was not detectable in 34 (33%), trace (1% to 5% of neoplastic cells) in 10 (9.7%), 1+ (6% to 25%) in 8 (7.8%), 2+ (26% to 50%) in 12 (11.7%), 3+ (51% to 75%) in 12 (11.7%), and 4+ (76% to 100%) in 27 (26.2%). The pattern of neoplastic cell staining was homogeneous in 14 patients (20.3%) and heterogeneous in 55 (79.7%). Carcinoma recurrence, overall survival, and event-free survival were not related to secretor status, BAA expression, or pattern of staining.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1994

T lymphocytes infiltrating renal cell carcinoma have a reduced expression of transferrin receptor.

T-cell responses have been reported to be impaired in cancer patients, and lymphocytes infiltrating human tumors (T-TIL) appear to be more affected than those in the peripheral blood. T-TIL display a poor proliferative response when compared to peripheral blood T (T-PBL) cells that show a strong response to all stimuli. Here we report that T-TIL from patients with renal cell carcinoma (RCC) also have a defect in transferrin receptor (TfR) expression that is not present in T-PBL cells. Immunocytometry studies (dual staining for CD3 epsilon and TfR) demonstrated that autologous T cells from the peripheral blood but not from the tumor expressed TfR following stimulation with IL2, anti-CD3 or PHA. Expression of TfR correlated with the capacity of T cells from the blood and tumor to proliferate. Gene expression studies using reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that TfR mRNA levels in T-TIL were undetectable or low relative to T-PBL following stimulation. The failure to detect TfR mRNA in T-TIL after stimulation was not due to a shift in kinetics of mRNA accumulation since TfR mRNA was not detectable at any of the times tested (4, 12, 24 and 36 hr). The defect in TfR gene expression is selective since IL2R alpha gene expression was induced in T-TIL. Because IL2 binding to its receptor results in TfR expression, the defect in TfR induction in T-TIL appears to be distal to IL2R alpha expression. Our studies illustrate another alteration in T-TIL that is not observed in T cells from the peripheral blood. The absence of TfR gene expression may contribute to the poor proliferative response of T cells from the tumor.

Base Sequence↗
PubMed1994

Phase II trial of dimethyltriazenoimidazole carboxamide in patients with metastatic carcinoid. A Southwest Oncology Group study.

BACKGROUND: The use of chemotherapy in patients with metastatic carcinoid tumors has been of limited value, and investigation of new agents is necessary. Previous reports have suggested that dimethyltriazenoimidazole carboxamide (DTIC) may have antitumor activity. METHODS: A Phase II trial to investigate the clinical response rate to DTIC in patients with metastatic carcinoid tumors was performed. DTIC was administered at low (650 mg/m2) or high (850 mg/m2) doses every 28 days. RESULTS: Sixty-three patients were entered into the study, and 56 were evaluable for toxicity and response. Toxicity was moderate, with the most common side effect being nausea and vomiting (88%). Nine patients (16%; 95% confidence interval, 8-28%) had partial responses, 5 of 25 receiving 850 mg/m2 and 4 of 31 receiving 650 mg/m2 of DTIC. Median survival time of all patients was 20 months. CONCLUSIONS: DTIC has minimal activity in patients with metastatic carcinoid tumors.

Adult↗