Clopidogrel resistance is associated with thromboembolic complications in patients undergoing neurovascular stenting.

BACKGROUND AND PURPOSE: Antiplatelet drug resistance has been associated with thromboembolic complications in patients after coronary stent placement. It has not been well-studied in patients who have neurovascular stent-placement procedures. This study aimed to analyze the relationship between antiplatelet drug resistance and neurovascular stent-placement complications. MATERIALS AND METHODS: A prospective data base of all patients treated at our institution was used to identify patients with neurovascular stent-placement procedures. During a 4.5-year period, all patients undergoing neurovascular stent placement were evaluated for aspirin and clopidogrel resistance by using the VerifyNow assay. During an observational phase, all patients received 75 mg of clopidogrel and aspirin (group A). During the intervention phase (group B), patients were given additional clopidogrel on the basis of the clopidogrel resistance assay. We assessed the development of thromboembolic complications within 30 days of the procedure in patients who were resistant-versus-nonresistant to clopidogrel. RESULTS: Of 96 patients who had neurovascular stent placement, 5.2% were resistant to aspirin and 36.5% were resistant to clopidogrel. Periprocedural thromboembolic complications were seen in 7 patients (7.3%). In a multivariate logistic regression model, clopidogrel resistance, higher diastolic blood pressure, and lack of statin use were significantly associated with periprocedural thromboembolic complication. There was a nonsignificant decrease in thromboembolic complications in patients whose clopidogrel dosage was tailored to the assay. CONCLUSIONS: In our series, clopidogrel resistance was associated with increased periprocedural thromboembolic complications from neurovascular stent-placement procedures. Targeting the clopidogrel dose to platelet inhibition assays may improve clinical outcomes and requires further study.

Ratio of cathepsin B to stefin A identifies heterogeneity within Gleason histologic scores for human prostate cancer.

BACKGROUND: Cathepsin B (CB), a lysosomal cysteine protease, is involved in degradation of extracellular matrix proteins and progression of tumor cells from one biological compartment to another in many solid organ cancers, including prostate cancer. Our objective was to identify patterns of distribution of CB and its endogenous cellular inhibitor stefin A in cryostat sections of frozen BPH and prostate cancer tissue samples and to define these patterns in relation to Gleason histologic scores, clinical stages, and serum total PSA levels. METHODS: We localized CB and stefin A in the same sections using polyclonal and monoclonal antibody immunoglobulin G (IgGs) against CB and stefin A using immunofluorescence and confocal microscopic techniques. Only cryostat sections of frozen prostates were used in localizations of CB and stefin A. RESULTS: Benign prostatic hyperplasia (BPH) showed similar localization patterns for CB and stefin A and a ratio of 1 was indicated by CB = stefin A. Confocal studies indicated that most CB and stefin A sites in BPH glandular cells overlapped as shown by the yellow fluorescence of their co-localization. We found considerable variability in individual localization of CB and stefin A within and between Gleason histologic scores for prostate cancers. This variability was also found in Gleason score 6 tumors that are otherwise considered similar histologically and morphologically. Negative control sections did not show localization of CB by FITC, stefin A by Cy3 or yellow fluorescence for co-localization. Our analysis of the ratio of CB to stefin A showed three patterns, namely CB = stefin A, CB > stefin A, and CB < stefin A, within each Gleason score evaluated by us. Confocal microscopy showed more sites of yellow fluorescence when the ratio was CB = stefin A than those found in CB > stefin A or CB < stefin A. Statistical analyses showed prostate cancer cases with ratios of CB > stefin A (P < 0.05) and CB < stefin A (P < 0.05) significantly different from normal prostate and BPH which had ratios of CB = stefin A. Regression analysis did not show any specific relationship between the ratio of CB to stefin A and Gleason scores, clinical stages, and serum total prostate specific antigen (PSA) levels in prostate cancers. Analysis of our data indicates that the homeostatic balance between the enzyme and inhibitor was altered even in Gleason histologic score 6 tumors that are usually considered histologically similar by glandular differentiation. CONCLUSIONS: We have shown that prostate cancer is a heterogeneous tumor within each Gleason histological score regardless of the progression indicated by lower to higher Gleason score tumors. The ratio of CB > stefin A would indicate a preponderance of enzyme that would favor degradation of extracellular matrix proteins and progression of tumor cells in biological compartments. These tumors are expected to be aggressive prostate cancers. In contrast, prostate tumors showing ratios of CB < stefin A and CB = stefin A are expected to be less aggressive prostate cancers. This is the first report to define heterogeneity within any Gleason score for prostate cancers by the ratios of CB to stefin A.

Binding of hydrogen sulfide by bismuth does not prevent dextran sulfate-induced colitis in rats.

Several lines of evidence suggest that ulcerative colitis could be caused by excessive bacterial production of H2S in the colon. A rodent model of colitis involves the feeding of nonabsorbable, carbohydrate-bound sulfate in the form of dextran sulfate or carrageenan. The observation that metronidazole blocks the development of this colitis suggested that the injurious agent could be a sulfur-containing compound (such as H2S) that is released during the bacterial metabolism of the nonabsorbed sulfate. We tested this possibility by feeding rats dextran sulfate, with or without bismuth subsalicylate, a compound that avidly binds H2S. Bismuth subsalicylate reduced the fecal release of H2S in dextran sulfate-treated rats to values well below that of controls. Nevertheless, all the animals developed colitis. We conclude that excessive H2S production does not play a role in the dextran sulfate model of colitis.

Temporal trends in survival after surgical resection of localized non-small cell lung cancer.

To test whether modern preoperative staging modalities and perioperative care improve survival after resection of localized non-small cell lung cancer (NSCLC), we retrospectively reviewed outcomes of 454 patients with NSCLC resected from 1947 through 1969 (designated pre-1970 cases), and 540 patients with cancers resected from 1981 through 1994 (designated post-1980 cases). Mean ages, histological subtypes, surgical stages, and types of surgical procedures differed significantly between the two groups. Compared with pre-1970 cases, post-1980 cases were older, had more adenocarcinoma and less squamous cell carcinoma, and had lesser proportions of advanced stage disease. Postoperative (day 30) mortality was significantly higher for resections of localized (stages 1 and 2) NSCLC prior to 1970. For patients surviving at least 30 days after surgery, subsequent survival after resection of localized NSCLC differed minimally between pre-1970 and post-1980 groups. We conclude that perioperative mortality after resection of localized NSCLC improved, but subsequent postoperative survival for these patients did not significantly improve over the 45-year period studied.

Dipeptidylpeptidase IV activities are elevated in prostate cancers and adjacent benign hyperplastic glands.

Dipeptidylpeptidase IV (DPP IV) is a serine exopeptidase that has been implicated in cell-extracellular matrix interactions and bioactive peptide/cytokine/growth factor metabolism. The objective of this study was to determine if DPP IV activities were changed with development of cancer in the prostate. DPP IV activity was measured in human prostate cancer and benign prostatic hyperplasia (BPH) tissues by biochemical assays with glycylprolyl-p-nitroanalide as substrate in tissue extracts (BPH, n = 8: cancer, n = 7; 2 with Gleason score 5 and 5 with Gleason score 7) and quantitative morphometry of histochemical activities with glycylproline-4-methoxy-beta-naphthylamide as substrate (BPH, n = 9: cancer, n = 13, 1 with Gleason score 4, 10 with Gleason score 6, 2 with Gleason score 8) in frozen-tissue sections. Data were analyzed by analysis of variance. The peptidase activity was detected in epithelial but not stromal cells of BPH and cancer tissues, and it was present as a single band of activity of approximately 160 kDa in electrophoretically separated activity blots of the extracts. DPP IV activity was increased approximately twofold in cancer versus BPH tissues as determined by biochemical and quantitative histochemical methods. In addition, DPP IV activity was increased to a similar extent in BPH glands associated with the cancers. These data indicate that DPP IV activity is increased not only in primary prostatic cancers but also in associated BPH glands, suggesting that there may be some local factors produced by cancer cells that influence adjacent BPH epithelial cells to positively affect the immediate growth environment of the cancer.

Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps.

Altered mucin glycosylation and the de novo appearance of gastric mucin antigens have been described in colonic adenomas. The purpose of our study was to determine if expression of the gastric mucin genes MUC5AC and MUC6 occurs in colorectal adenomas and whether this correlates with histopathologic criteria of malignant potential. Immunohistochemical staining using antibodies against MUC5AC and MUC6 tandem repeat synthetic peptides was performed on specimens of normal colon mucosa (n = 26), hyperplastic polyps (n = 9) and adenomatous polyps (n = 111). Mucin mRNA levels were determined using RNase protection assays using riboprobes corresponding to unique non-repetitive sequences. MUC5AC and MUC6 staining were rarely detected and of low intensity in normal colon and hyperplastic polyps. The number of immunoreactive polyps and intensity of MUC5AC and MUC6 staining were greatest in larger adenomas of moderate villous histology and dysplasia. MUC5AC and MUC6 staining tended to decrease in highly villous polyps with severe dysplasia. Increased MUC5AC mRNA levels were found in 26/45 of adenomas tested compared with 0/9 normal colon specimens. MUC6 mRNA levels were found in 20/45 of adenomas compared with 1/9 normal colon specimens. MUC5AC and MUC6 mRNA were present more frequently and at higher levels in polyps with intermediate stages of size, villous histology and dysplasia. We conclude that aberrant expression of MUC5AC and MUC6 mucin genes is likely responsible for an expanded repertoire of mucin antigen expression in colorectal neoplasia.

The relationship of cathepsin B and stefin A mRNA localization identifies a potentially aggressive variant of human prostate cancer within a Gleason histologic score.

Cathepsin B (CB) is involved in degradation of extracellular matrix proteins during tumor progression in human solid organ tumors (such as colorectal, bladder, and breast cancers), including human prostate cancer. Its activities are regulated by endogenous inhibitors (such as stefins or cystatins). Increased expression of cathepsin B message, protein, and membrane association have been linked to malignancy, but there are very few studies of their mRNA expression in prostate cancer using in situ hybridization techniques. Our objective was to determine the relationship of CB and stefin A (cystatin A) mRNA localization to the Gleason grading system for histologic scores in the hope of distinguishing aggressive and less aggressive variants of prostate cancer. We used a 25-base biotinylated oligonucleotide CB cDNA antisense probe to localize CB message and a 27-base biotinylated oligonucleotide stefin A cDNA antisense probe to localize stefin A message. Prostate samples from 41 prostatectomy patients were collected along with their pre-surgery serum PSA levels and clinical stage of the disease. Sections prepared from frozen prostate tissue samples were hybridized with the CB and stefin A and control pBR 322 probes using techniques reported by Sinha et al. [1] and their distribution quantitated by an image analysis system. Prostate sections treated with RNAse before hybridization or incubated with the pBR 322 control probe showed little or no reaction products, confirming that localization of CB and stefin A probes was specific. In prostate cancer, the reaction products were found in neoplastic and invasive cells and occasionally in stromal cells. The ratios of CB to stefin A were similar in normal prostate and benign prostatic hyperplasia (BPH) whereas they varied consistently within and between Gleason histologic scores for prostate cancer. These variations showed three localization patterns; namely, prostate cancers with higher levels of CB than stefin A, lower levels of CB than stefin A, and similar levels of CB and stefin A. All three patterns and ratios for CB and stefin A were found in prostate samples (22/41) represented by the Gleason histologic score 6 tumors. In these tumors, serum PSA levels ranged from 1 to 78 ng/ml and prostate cancers showed B, C, and D clinical stages. There was no correlation of CB/stefin A ratio and serum PSA values or clinical stage in a limited number of prostate cancer cases. Our data showed that there were prostate cancer cases within Gleason histologic scores which expressed high, similar, and low levels of CB when compared to stefin A. We postulate that prostate cancer cases showing higher levels of CB compared to stefin A probably represent an aggressive variant of this cancer within any one Gleason histologic score. If this is the case, aggressive variants of prostate cancer would occur within Gleason scores 3 to 10 even though higher scores are usually considered more aggressive forms of prostate cancers. Since our study is based upon a very limited number of frozen prostate samples, we emphasize that a larger series of archival prostate cancer samples along with their survival data should be analyzed to establish any relationship of CB/stefin A ratio and aggressive variants of this cancer. Therefore, our conclusion is tentative. Our study provides a partial explanation for differences in the clinical course of prostate cancer in patients. This is the first study to show that determination of CB and stefin A mRNA ratios may lead to identification of aggressive and less aggressive variants of prostate cancer within a Gleason histologic score.

Immunocytochemical localization of an immunoconjugate (antibody IgG against prostatic acid phosphatase conjugated to 5-fluoro-2'-deoxyuridine) in human prostate tumors.

Current chemotherapeutic and/or endocrine treatments for adenocarcinoma of the prostate (CaP) do not selectively target neoplastic prostate cells. Therefore, new approaches are needed to improve treatment for prostate tumors. We hypothesized that because of the specific binding of antibody immunoglobulin G (IgG) against human prostatic acid phosphatase (PAcP), PAcP-IgG could function as a carrier protein for the conjugated chemotherapeutic drugs and that the immunoconjugate would then selectively localize (bind) to epithelial cells of human prostate tumors, but not to epithelial cells of other solid organs. Our objective was to test this hypothesis using human prostate, colon, and kidney tissue samples and human prostate pieces incubated in short-term organ culture. We used derivatives of 5-fluorouracil labeled with fluorescein isothiocyanate (FITC) and rabbit anti-PAcP-IgG tagged with CY3/rhodamine alone or as an immunoconjugate. Localization of PAcP-IgG alone and the immunoconjugate in prostate produced similar and specific immunostaining in prostate epithelial cells and their tumors, but not in epithelia of colon and kidney tissue sections or in prostate sections-treated with normal rabbit serum. Confocal microscopy showed co-localization of CY3 and FITC of the immunoconjugate in the same group of prostate epithelial cells and their tumors. Organ culture studies showed that human prostate tissue samples incubated with normal rabbit serum did not show any fluorescence whereas those cultured with PAcP-IgG immunoconjugate showed fluorescence in glandular epithelial cells. The later study also showed that in organ culture the immunoconjugate had penetrated and labeled prostate glands internal to the cut surfaces. Drug labeled with FITC did not localize specifically in the prostatic epithelium. Analysis of our data has shown that PAcP-IgG was needed for specific localization of the immunoconjugate in prostate glands. We conclude that PAcP-IgG was essential for delivery and binding of the drug in human prostate. This is the first report to show that PAcP-IgG-5-Fu-2'-d-based immunoconjugate was selective and specific to epithelial cells of human prostate and its tumors, as revealed by organ culture, immunocytochemical, and confocal microscopic techniques.

Altered mucin core peptide immunoreactivity in the colon polyp-carcinoma sequence.

Altered mucin glycosylation occurs in colonic adenomas and can correlate with risk for malignant transformation. The purpose of this study was to determine if immunoreactivity of core tandem repeat peptides of specific mucin genes correlates with histopathologic criteria of malignant potential in the colon. Expression of MUC1, MUC2, and MUC3 core tandem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and invasive cancer (n = 19). An immunohistochemical scoring system that takes into account specimen heterogeneity and yields an integrated numerical score subject to statistical analysis was used. RNA message levels from tubular and tubulovillous adenomas (n = 13), normal colon (n = 12), and moderately differentiated adenocarcinomas (n = 8) were determined using RNA slot blot analysis with mucin-specific cDNA probes. MUC1 staining was rarely present in normal colon. MUC2 immunoreactivity was limited to goblet cells in most normal colonic crypts, and MUC3 staining was weakly expressed in the upper crypt regions only. In comparison with normal and hyperplastic specimens, MUC1 and MUC3 immunoreactivity scores were significantly increased in adenomas of increasing villous histology, size, and dysplasia. MUC2 scores were significantly increased in adenomas of greater villous histology and size. Comparable MUC1, MUC2, and MUC3 mRNA levels were present in adenomas and normal colon, whereas mucin mRNA levels were decreased in adenocarcinomas. We conclude that enhanced immunoreactivity of MUC1, MUC2 and MUC3 mucin tandem repeats occurs in adenomatous polyps and is associated with an increased risk for malignant transformation.

Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in response to mucosal disease.

One-third of convalescent-phase serum samples (6 of 18) from patients with Clostridium difficle-associated diarrhea demonstrated neutralization of the clostridial enterotoxin, toxin A. Although appreciable amounts of toxin A-specific immunoglobulin G (IgG) and IgA were present in these sera, the ability to neutralize the cytotoxic activity of toxin A on OTF9-63 cells in vitro was confined to the IgA fraction and the IgA1 subclass in serum samples from all six patients. In contrast to the patients with C. difficile diarrhea, this activity was present in both the IgA and IgG fractions in sera from two C. difficile-infected patients without diarrhea, one of whom presented with a splenic abscess. Sera and purified IgA which neutralized the cytotoxicity of toxin A on OTF9-63 cell cultures in vitro also neutralized the enterotoxicity of toxin A in rabbit ileal loops in vivo. This activity was not Fc dependent, since IgA retained neutralizing activity after pepsin digestion and F(ab')2 purification. The transition from nonneutralizing toxin A-specific IgA in the acute-phase sera to neutralizing specific IgA in the convalescent-phase sera was accompanied by a shift from a polymeric to a predominantly monomeric form of specific IgA. However, the neutralizing activity in convalescent-phase sera was present as both monomeric and polymeric IgA. Convalescent-phase sera from other patients with C. difficile diarrhea that failed to neutralize toxin A also failed to produce a predominantly monomeric-form specific IgA response. We conclude that serum IgA, not IgG, characteristically neutralizes toxin A in patients with C. difficile diarrhea who develop neutralizing systemic responses. This neutralization of an enteric bacterial toxin is a unique and selective role for serum IgA which provides a novel functional link between the systemic and mucosal immune systems.

Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on human gut mucosa.

Mevalonic acid is an important biochemical intermediate in cholesterol synthesis and other processes involved in cell replication. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the enzyme which catalyzes mevalonic acid synthesis. To determine whether a potent competitive inhibitor of this enzyme, the drug simvastatin, may have an adverse effect on enterocyte cell replication and cholesterol metabolism, small intestinal biopsies from nine hypercholesterolemic subjects were obtained before and during treatment with simvastatin as a lipid-lowering agent. Histologic review of biopsies in a blinded manner detected no change in ratio of villous length to crypt length or in mitotic index which might indicate altered cell replication. Similarly, no significant change in measured activity of HMG-CoA reductase activity was observed. In spite of the high exposure of jejunal mucosal cells to this potent competitive inhibitor of a key enzyme, no adverse effect on growth could be detected.

Leukocytosis and large cell lung cancer. A frequent association.

In a retrospective study of 105 patients with non-small cell lung cancer during a 5-year period, 43 had leukocytosis. In 19 of the 43 patients, no clear cut etiology for the leukocytosis was apparent and it was attributed to the tumor itself. In these 19 patients, absolute neutrophilia was detected in 13, eosinophilia was present in three, and eleven exhibited concomitant thrombocytosis. Tumor-associated leukocytosis occurred predominantly, and eosinophilia exclusively, in patients with large cell pulmonary neoplasms. These results suggest an unusual myeloproliferative stimulus in this type of cancer. It may result from tumor cell production of hemopoietic growth factors such as granulocyte-macrophage colony-stimulating activity; however, additional studies are needed to elucidate the underlying mechanism(s), and to determine whether this is a peculiar characteristic of the cells that comprise large cell undifferentiated carcinoma of the lung.

Neuroendocrine carcinoma of the larynx.

Neoplasms of the larynx showing neuroendocrine differentiation are uncommon, with less than 100 previously reported cases. These tumors encompass subcategories that have been designated heretofore as "malignant carcinoid" and "oat cell carcinoma" and have been associated with ectopic production of neuropeptides and biogenic amines. We report a case of neuroendocrine carcinoma that arose in the epiglottis in an elderly man, metastasized widely, and was responsible for death. Immunohistochemical studies showed the presence of serotonin, calcitonin, ACTH, met-enkephalin, chromogranin, and neuron-specific enolase within tumor cells, although clinical endocrinopathy was absent. This case is used as a focus for discussion of the spectrum of neuroendocrine tumors of the head and neck, including recommended treatment approaches for such neoplasms.

Scintigraphic findings in chronic actinomycosis osteomyelitis and associated soft tissue infection.

Scintigraphic findings are reported in a patient with actinomycosis osteomyelitis and soft tissue infection to illustrate the need to understand the mechanism of localization of the radiopharmaceutical to accurately assess the clinical pathology.

Lung disease in long-term cigarette smokers with and without chronic air-flow obstruction.

Despite the established role of cigarette smoking in the causation of chronic air-flow obstruction (CAO), only a small proportion of regular cigarette smokers develop significant clinical disease. We compared emphysema severity as well as pathologic and morphometric features of the peripheral conducting airways and the muscular pulmonary arteries among 3 groups of older subjects. These groups included lifelong nonsmokers (NSM), regular smokers without severe disease (SM), and smokers with an established diagnosis of CAO (SM-CAO). For most pathologic features examined there was an orderly progression in severity when comparing SM to NSM and SM-CAO to SM. Emphysema severity and scores for peripheral airways disease, except for goblet cell metaplasia, better distinguished SM-CAO from SM than did measures of bronchiole lumenal caliber. Within the SM-CAO group, the premortem percent predicted forced expiratory volume in one second (FEV1) correlated significantly with emphysema severity (r = 0.74), with average bronchiole diameter (r = 0.54), with the proportion of bronchioles with diameters less than 400 mu (r = 0.51), but not with any of the scores for bronchiolar disease. However, within this group no morphologic or pathologic feature of the small airways was an independent predictor of ventilatory function beyond that of emphysema alone. When compared with those from NSM, histological sections from SM-CAO lungs contained approximately twice as many fully muscularized artery profiles 0 to 300 mu in diameter, the arterial medial muscle layer was doubled in thickness, and the amount of arterial intimal fibrosis was tripled.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of histologic type on survival after curative resection for undifferentiated lung cancer.

Undifferentiated carcinoma of the lung carries a worse prognosis overall than other cell type, but it is unclear whether these tumors represent a homogeneous group with uniformly poor survival. This study identifies certain histologic subtypes of large cell and small cell undifferentiated carcinoma which have a better prognosis after curative resection than other similarly treated undifferentiated carcinomas. From 1947 through 1975, a total of 2,352 patients with lung cancer were admitted to one hospital. Follow-up to death was available in 98%. Pathological material was reviewed from 1,979 cases by a team of three pathologists during a single 6 month period without knowledge of clinical outcome. Curative resection was carried out in 632, with 170 (27%) 5 year survivors. Small cell cancer occurred in 481 patients and nine (1.6%) survived 5 years. Curative resections were performed in 34 with polygonal small cell carcinoma, 20 with normal lymph nodes and 14 with diseased lymph nodes. Seven survived 5 years (21%), six of 20 with normal and one of 14 with diseases lymph nodes. Eleven with nonpolygonal small cell carcinoma (eight oat cell, three fusiform) (five normal, six diseases nodes) underwent curative resection, with no survivors. Large cell carcinoma occurred in 151 and 19 survived 5 years. Curative resection was performed in 24 having large cell carcinoma with stratification (16 normal, eight diseased nodes), and 12 (50%) survived 5 years. In 26 with nonstratified large cell carcinoma undergoing curative resection (18 normal, eight diseases nodes); six (23%) survived 5 years (chi 2 = 4.06 p less than 0.05). Thus patients with resectable polygonal small cell carcinoma appear to have a better prognosis than those with nonpolygonal small cell carcinoma, and their prognosis approaches that of all patients with resectable lung cancer. Patients having resectable large cell carcinoma with stratification have a significantly better prognosis than those with nonstratified large cell carcinoma. Patients with these subtypes should therefore not be denied an attempt at curative resection because of the diagnosis of undifferentiated lung cancer.

The production of malignant tumors of the lung and pleura in dogs from intratracheal asbestos instillation and cigarette smoking.

Nine dogs were given early intratracheal instillations of crocidolite asbestos for periods up to three years. The maximum dose totalled 66 mg/kg. In addition, seven of these dogs smoked nine cigarettes per day, five days per week for six years. A malignant pleural and/or peritoneal mesothelioma developed in six of these dogs, and adenocarcinoma of the lung developed in four, one of which had areas of squamous differentiation. The first animal died of a malignant tumor six years after the onset of exposure, and the last animal died eight years after the onset.

Chemotherapy for small cell bronchogenic carcinoma: CCNU and doxorubicin compared to CCNU, doxorubicin, vincristine, and procarbazine.

Forty consecutive patients with small cell bronchogenic carcinoma were treated. The first 18 patients were treated with CCNU and doxorubicin (Adriamycin) (CA). The next 22 patients were treated with CCNU, doxorubicin, procarbazine, and vincristine (CAPO). Patient characteristics were similar. The partial plus complete response rate was 55% (ten of 18 patients) in the CA group compared to 41% (nine of 22 patients) in the CAPO group. The median survival from treatment was 28 weeks in the CA group compared to 33 weeks in the CAPO group. There were no drug-related deaths among the patients receiving CA compared to two definite and three probably drug-related deaths among the patients receiving CAPO. The addition of procarbazine and vincristine to CA for the treatment of small cell bronchogenic carcinoma resulted in increased toxicity and no survival benefit.