Cytomegalovirus colitis in acquired immunodeficiency syndrome--a chronic disease with varying manifestations.

A patient with acquired immunodeficiency syndrome and cytomegalovirus colitis is described. The colitis is more chronic and less severe than earlier descriptions. This case presents different and more varied endoscopic findings than previously reported.

Phase II clinical evaluation of intravenous 4'-(9-acridinylamino)methanesulfon-m-anisidide in colorectal cancer.

Thirty-five patients with measurable metastatic colorectal cancer received 4'-(9-acridinylamino)methanesulfon-m-anisidide (AMSA) on a 3-day intravenous schedule repeated every 3 weeks. There were 17 previously untreated patients and 18 patients who had disease progression on several regimens containing 5-fluorouracil. Good-risk patients received an initial daily AMSA dose of 40 mg/m2; poor-risk patients received an initial daily dose of 30 mg/m2. There were no complete or partial remissions. Ten patients achieved disease stabilization, 24 had disease progression and one patient was lost to follow-up. The most common toxicity associated with AMSA therapy was myelosuppression, with a greater effect on neutrophils than platelets. Median (range) lowest neutrophils and platelet counts X 10(3)/mm3 were 1.2 (0-5.0) and 209 (50-413), respectively. Myelosuppression was pronounced in patients with abnormalities of liver function. Other toxicities were negligible, although one patient developed an episode of cardiac arrhythmia which may have been secondary to AMSA therapy.

Phase II evaluation of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU, NSC 95466) in patients with metastatic colorectal cancer.

Thirty-two patients with measurable metastatic colorectal cancer refractory to 5-fluorouracil-containing regimens received PCNU (1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea, NSC 95466) on a single-day I.V. schedule administered every 6 weeks. Good-risk patients received PCNU at the starting dose of 100 mg/m2, while patients who had received radiotherapy or myelosuppressive drugs such as mitomycin C received an initial dose of 75 mg/m2. There were two partial remissions. Fifteen patients including four with minor tumor regression had disease stabilization. The dose-limiting toxicity was myelosuppression, with thrombocytopenia being more severe than neutropenia. The myelosuppression occurred late in the treatment cycle (days 25-32), was more severe with repeated treatments, and was more severe in patients who had a poor bone marrow reserve. Other toxicities were mild and infrequent. PCNU administered by the single-dose I.V. schedule as used in this study has very modest antitumor activity against colorectal cancer in humans.

Phase I--II study of the combination of 5-FU, doxorubicin, mitomycin, and semustine (FAMMe) in the treatment of adenocarcinoma of the stomach, gastroesophageal junction, and pancreas.

One hundred and fifteen patients with advanced gastrointestinal cancer (stomach cancer, 42 patients; gastroesophageal junction cancer, ten; pancreatic cancer, 32; and other upper gastrointestinal cancers, 31) were treated with a combination chemotherapy regimen consisting of 5-FU, doxorubicin, mitomycin, and semustine (methyl-CCNU) (FAMMe). Of the 31 patients with stomach cancer who were evaluable for response and had had no previous chemotherapy, 12 (39%) achieved complete or partial remission. One of eight (12%0 patients with gastroesophageal junction cancer and five of 23 (22%) patients with pancreatic cancer achieved a partial remission. The median duration of survival for all patients with adenocarcinoma of the stomach was 7.1 months. The median duration of survival for responding patients with stomach cancer was 13.6 months, and the median survival for nonresponding patients was 6.1 months. FAMMe chemotherapy was generally well-tolerated and can be administered in adequate doses without producing prohibitive myelosuppression. The starting dose should be reduced for patients greater than or equal to 70 years old or for patients who have received pelvic or vertebral radiation therapy. FAMMe is effective against advanced gastric cancer; however, because this was not a randomized comparative study of the relative effectiveness of FAMMe and FAM (5-FU, doxorubicin, and mitomycin), no recommendation for the use of one regimen instead of the other for advanced adenocarcinoma of the stomach can be made. FAMMe chemotherapy cannot recommended for advanced adenocarcinoma of the pancreas and gastroesophageal junction.

Sequential phase II studies of chemotherapy for colorectal cancer with 5-fluorouracil and vindesine with or without methyl-1,3 cis(2 chloroethyl)-1-nitrosourea.

Vindesine, a newer vinca alkaloid, has been demonstrated to have activity against colorectal cancer during phase I studies. This report describes the results of two phase II trials in which vindesine was administered with 5-fluorouracil (5-FU) or in combination with 5-FU and methyl-1,3 cis(2 chloroethyl)-1-nitrosourea (MeCCNU). One of 16 patients (6%) given 5-FU-vindesine, and 4 of 31 (13%) patients in the 5-FU-vindesine-MeCCNU group achieved partial response (PR). Stable disease was observed in 50% of the 5-FU vindesine and 48% of the 5-FU-vindesine-MeCCNU group. In each treatment group, survival of respondents and those with stable disease was statistically superior (p less than 0.02) to that of those with progressive disease; there was no difference however, in overall survival between the two treatment groups and no enhancement of survival compared to published reports of results with 5-FU alone. No chemotherapy-related deaths occurred and both treatment regimens were well tolerated. Myelosuppression, which occurred with equal (50%) frequency in both regimens, was the major dose-limiting toxicity. MeCCNU increased the incidence of gastrointestinal toxicity. Vindesine neurotoxicity occurred in approximately 4% of the evaluable courses in each group. Combination therapy with 5-FU vindesine with or without MeCCNU in the dosages administered did not significantly increase the activity of 5-FU. Further evaluation of vindesine will require dosage modification.

Pancreatic carcinoma in a ten-year survivor of acute myeloblastic leukemia.

Adenocarcinoma of the pancreas developed in a young man who was a 10-year survivor of acute myeloblastic leukemia (AML). His extensive cytotoxic chemotherapy for AML is reviewed along with a discussion of its possible oncogenic effects. Other case reports of second malignant neoplasms (SMN) following acute leukemia are cited; available data suggest that the overall risk of SMN in AML may be in the range of 6%. While our patient's second malignancy may have been a chance association, his and other cases of pancreatic carcinoma in young survivors of hematologic neoplasia suggest that the cytotoxic treatment may have had a role in the pathogenesis of the pancreatic carcinoma.

Chemotherapy for colorectal cancer with a combination of PALA and 5-FU.

Fifty-one previously untreated patients with advanced, measurable colorectal cancer were randomized to receive single doses of PALA and 5-FU either weekly (24 patients) or daily for 5 days every 4 weeks (27 patients). In both schedules the daily dose of PALA was administered iv over 1 hour, while the dose of 5-FU was administered iv over 30 minutes, starting 3 hours after completion of the PALA dose. Doses of both drugs were changed simultaneously, based on toxic effects. Partial responses were seen in four of 24 evaluable patients receiving the weekly regimen and in three of 26 patients receiving the 5-day regimen. Skin rash, mucositis, and diarrhea were the dose-limiting toxic effects in both treatment regimens. These toxic effects were more common and severe at higher doses and on the weekly schedule. Myelosuppression was mild and moderate, the doses and schedules used in this study did not significantly increase the activity of 5-FU. Further evaluation of these doses and schedules for activity against colorectal cancer is not warranted.

Transport characteristics of papain-treated brush-border membrane vesicles. Non-involvement of gamma-glutamyltransferase in leucine transport.

Papain treatment of isolated brush border membrane vesicles was carried out to correlate directly the solubilization of gamma-glutamyltransferase with the uptake of leucine. Digestion of membrane vesicles with either soluble or gel-complexed papain resulted in nearly complete removal of gamma-glutamyltransferase. However, the treated vesicles exhibited increased specific activity of leucine and glucose uptake, indicating the non-involvement of the transferase in leucine transport. The partial purification of amino acid and sugar transport function was better controlled with gel-complexed papain. In contrast to the digestion with soluble papain, the treatment with gel-complexed papain did not modify the diffusional components for solutes and ions and did not alter the intravesicular volume. It appears that controlled papain-digestion, resulting in nearly a 2-fold purification of the transport function with high reproducibility and quantitative recovery of uptake, should be useful in future attempts to purify the 'carrier' proteins.

Q fever endocarditis in the United States.

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.