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Y Z Patt

Publications and source records attributed to Y Z Patt.

At least 19 recordsLinked to original sources
PubMed1992

Phase II study of didemnin B in advanced colorectal cancer.

Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patients with measurable, unresectable colorectal cancer were treated with Didemnin B at an initial dosage of 3.47 mg/m2 over 30 minutes administered by intravenous infusion every 28 days; the dosage was altered in accordance with the toxicity observed, with only one patient requiring a dosage reduction for pronounced nausea and vomiting. No hematologic or nonhematologic toxicity developed. No complete or partial responses were observed. These results do not compare favorably with results of treatments using other single agents or combinations that are currently available for the treatment of advanced colorectal cancers. However, because of the tolerable levels of toxicity experienced by in our patients, it is possible that an insufficient dose of the medication was delivered. We concluded that Didemnin B is not active against of colorectal cancers at the dosage and schedule at which it was administered in this study.

Adenocarcinoma↗
PubMed1991

Phase II study of intravenous 6-thioguanine in patients with advanced gastric carcinoma.

In a phase II study, 18 patients with advanced gastric carcinoma were treated with intravenous 6-thioguanine. A 30-minute infusion of 55 mg/m2 (starting dose) was administered once a day for 5 consecutive days, the courses being repeated every 5 weeks. A median of 2 courses (range, 1-4) was administered. Among the 18 patients, 17 having measurable cancer and optimum follow-up were fully assessable for response. None of the patients achieved a complete or partial response. One patient achieved a transient minor response (15 weeks) of the primary gastric carcinoma but the metastatic carcinoma was unchanged. One patient had no change in his measurable carcinoma, and the other 15 patients had progressive disease while receiving intravenous-6-thioguanine. Myelosuppression, although frequent, was mild to moderate at these doses and did not result in significant morbidity. Nonhematologic toxicities were also mild. Our data suggest that intravenous 6-thioguanine given at this schedule is ineffective in previously untreated patients with advanced gastric carcinoma.

Adult↗
PubMed1991

Phase II study of intravenous 6-thioguanine in patients with advanced carcinoma of the pancreas.

In a phase II study, 32 patients with advanced pancreatic carcinoma were treated with intravenous 6-thioguanine. A 30-min infusion of 55 mg/m2 (starting dose) was administered once a day for 5 consecutive days, the course being repeated every 5 weeks. A median of two courses (range, 1-10) was administered. Among the 32 patients, 30 having measurable cancer and optimum follow-up were fully assessable for response. One patient achieved a partial response of extensive liver metastases (12+ months), and another patient had a transient minor response (5 weeks). Cancer in 27 of 30 assessable patients progressed during intravenous 6-thioguanine treatment. Myelosuppression, although frequent, was mild to moderate at these doses and did not result in significant morbidity. Nonhematologic toxicities were also mild. Our data suggest that intravenous 6-thioguanine given at this schedule is ineffective in previously untreated patients with advanced carcinoma of the pancreas.

Adult↗
PubMed1991

Arterial chemotherapy in the management of colorectal cancer: an overview.

We have discussed the role of arterial therapy in patients with various stages and types of colon cancer. Arterial therapy is probably not useful as an adjuvant therapy for Dukes' C colon cancer. It may, however, play a role among patients with incomplete resection of liver metastases (positive margins). A randomized trial is needed to determine the role of arterial therapy in patients who have undergone complete resection of liver metastasis. Arterial therapy does not seem justified for patients with recurrent pelvic tumors. For nonresectable liver metastases, hepatic arterial therapy induces a higher response rate than does intravenous treatment. It may also improve performance status and offer additional palliation to patients who have failed systemic chemotherapy. are refractory to systemic chemotherapy may be candidates for palliative hepatic arterial chemotherapy even out of the context of a clinical trial. Asymptomatic patients with nonresectable liver metastasis who are refractory to systemic chemotherapy should be enrolled in phase I-II arterial chemotherapy trials designed to identify optimal treatment regimens. Previously untreated asymptomatic patients wishing treatment may be enrolled in a new multi-institutional phase III trial being designed to compare contemporary systemic chemotherapy with less toxic arterial therapy and combined arterial and systemic therapy. Such a new trial will have to avoid any cross-over between arms to determine the true impact of arterial therapy on survival. Regional arterial chemotherapy tries to extract the "extra mile" from marginally active drugs that have a steep dose response curve by increasing tumor drug exposure. Increased drug concentrations in the tumor may be accomplished by means of the blood vessel-to-tumor concentration gradient. The technology to achieve such a gradient has involved percutaneous hepatic arterial catheters, implantable infusion pumps or ports, and external pumps. The most economic hepatic arterial delivery system for protracted arterial FUdR is an infusion pump. Despite good pharmacological rationale, an improved response rate, and good evidence for effective palliation in advanced disease, hepatic arterial therapy has not improved survival when compared with systematic intravenous treatment. Possible explanations include the following: (1) poor study design that allowed patients to cross over between arms: (2) inadequate arterial chemotherapy combination; (3) inadequate arterial chemotherapy schedule; (4) hepatobiliary toxicity levels that required cessation of hepatic arterial therapy and allowed the emergence of resistant tumor clones; and (5) systemic progression of disease. Only time will tell whether improved chemotherapy and the design of a new phase III trial will establish a beneficial role for upfront hepatic arterial therapy in asymptomatic patients with colon cancer metastatic to the liver.

Antineoplastic Agents↗
PubMed1990

Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma.

A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy. A total of 65 courses was given, with the median being 2 (range, 1-9 courses). None of the patients achieved a partial or complete response; however, 3 patients achieved a minor response and 14 had stable disease. The frequent toxic effects of DFMO included thrombocytopenia (which was dose-limiting), malaise, nausea, vomiting, reversible hearing loss, and diarrhea. Our data suggest that continuous-infusion DFMO therapy is feasible and results in only mild gastrointestinal toxicity. Although DFMO proved to be ineffective as a single agent in this trial, it could probably best be used in combination with cytotoxic agents known to enhance its antitumor activity in a preclinical setting.

Carcinoma↗
PubMed1990

Metastatic colorectal cancer: radioimmunoscintigraphy with a stabilized In-111-labeled F(ab')2 fragment of an anti-CEA monoclonal antibody.

Metastatic colorectal cancer was detected with stabilized F(ab')2 fragments of ZCE-025, an anti-carcino-embryonic antigen (CEA) monoclonal antibody (MoAb). The fragments were prepared by cross-linking Fab' with a bifunctional cross-linking agent, bis-(maleimido)methyl ether. The authors labeled 2 mg of ZCE-025 with 5 mCi (185 MBq) of indium-111 and injected the material intravenously, either alone or with unlabeled F(ab')2, into 16 patients. Lesion detection, pharmacokinetics, and relative body distribution were evaluated and compared with those of the intact immunoglobulin (IgG1) antibody. Stabilized F(ab')2 fragments were more useful than the intact antibody in detection of lesions: Overall sensitivity of F(ab')2 fragments for all the patients was 79.4%, whereas overall sensitivity of the intact IgG1 antibody was 32%. This anti-CEA-stabilized F(ab')2 fragment may be a powerful diagnostic tool that can achieve higher sensitivity at smaller protein doses than the intact IgG1 antibody.

Antibodies, Monoclonal↗
PubMed1990

Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

Adult↗
PubMed1990

Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma.

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.

Colorectal Neoplasms↗
PubMed1990

Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases.

We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma (18 with colon cancer, one with breast cancer, and one with Hodgkin's disease) and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.

Adenocarcinoma↗
PubMed1990

A phase II study of trimetrexate therapy for metastatic colorectal carcinoma.

Thirty patients with measurable metastatic colorectal carcinoma who had not received prior systemic therapy for advanced disease were treated with trimetrexate, a methotrexate analog. Trimetrexate was administered at a median daily dose of 15 mg/m2 (range, 6-22 mg/m2) intravenously for five days every three weeks. No patient achieved a complete or partial response, although minor responses of brief duration occurred in eight patients. The drug was generally well tolerated, thus permitting frequent dose escalations. Common toxic effects included mucositis, dermatitis, and myelosuppression. Our data suggest that trimetrexate given at these doses and in this schedule is not active against colorectal carcinoma.

Adult↗
PubMed1989

Phase I trial of recombinant human gamma-interferon and recombinant human tumor necrosis factor in patients with advanced gastrointestinal cancer.

Recombinant human gamma-interferon and recombinant human tumor necrosis factor are two representatives of a new class of antineoplastic agents. In vitro studies have suggested synergistic cytotoxic activities when the agents are combined. We report a phase I study of these two agents when administered daily for 5 consecutive days every 2 weeks in patients with advanced gastrointestinal cancers. Toxicity resulting from these agents was significant with hyperbilirubinemia representing the dose-limiting toxicity. Significant, although transient, myelosuppression was also observed. The maximal tolerated doses were 150 micrograms/m2/day for 5 days for each agent. Suggestive antineoplastic activity in biliary and pancreatic cancer was observed. Phase II trials of this combination are currently in progress.

Adult↗
PubMed1989

Differential tumor regression in patients with bilobar hepatic metastases and dual arterial supply: evidence supporting the advantage of intra-arterial over intravenous route of drug delivery.

Two patients with bilobar liver metastases were characterized by dual arterial blood supply to the liver. Treatment of both patients by the administration of chemotherapy, selectively via the arterial branches supplying the respective hepatic lobes bearing the metastases, resulted in differential tumor regression/progression. Thus, while the metastases borne by the arterially infused lobe regressed, the counterpart in the other (systemically infused) lobe showed marked progression. This phenomenon lends strong support to the notion that arterial infusion of chemotherapy in cases of regionally predominant (or confined) neoplastic disease, i.e., in the liver, is superior to the intravenous administration of similar drugs.

Adult↗
PubMed1988

Regression of ocular melanoma metastatic to the liver after hepatic arterial chemoembolization with cisplatin and polyvinyl sponge.

Thirty patients with ocular melanoma metastatic to the liver were treated by hepatic arterial chemoembolization using an admixture of cisplatin and polyvinyl sponge. Tumor regression was complete in one patient and partial (greater than 50%) in 13 patients. The total response rate was 46%. The median survival for the entire group was 11 months (95% confidence interval, nine to 18 months). Treatment-related morbidity was short-lived and included primarily severe upper right quadrant abdominal pain, transient paralytic ileus, and nonicteric hepatitis. Hepatic arterial chemoembolization provided effective palliation, with good-quality survival among 46% of patients with ocular melanoma metastatic to the liver.

Adult↗
PubMed1988

Hepatocellular carcinoma. A retrospective analysis of treatments to manage disease confined to the liver.

The histories of 73 patients with hepatocellular carcinoma (HCC) confined to the liver who were seen at M. D. Anderson Hospital between January 1976 and December 1983 were reviewed. In 18 patients the tumor was resected either at the outset or after the patients' response to chemotherapy; nonsurgical treatments consisted of hepatic arterial infusion (HAI) in 10 patients and intravenous (IV) therapy in four patients. Patients who had resection were younger, and their liver functions and performance status were better than the IV and HAI groups. Their median survival was 46 months. Of the patients who had nonresectable tumors, 28 received chemotherapy by HAI and 27 received IV therapy. Of the 28 patients in the HAI treatment group, 25 received uniform infusion of floxuridine (FUDR, Roche, Australia), doxorubicin (Adriamycin), and mitomycin C (FUDRAM). Of the 27 patients in the IV treatment group, 15 received 5-fluorouracil (5-FU) and doxorubicin-containing regimens; in 11 patients 5-FU was combined with other agents. The HAI and IV treatment groups were similar in age and ethnicity, performance status, serum alpha-fetoprotein levels, liver function, presence of hepatitis B antigen, and presence or absence of cirrhosis. The median survival was 9 months for HAI-treated patients and 5 months for the IV-treated group. The statistical differences were resection versus HAI, P less than 0.01; resection versus IV, P less than 0.01; HAI versus IV, P less than 0.01. Thirteen of 18 patients who had resections, six of 28 patients treated with HAI, and two of 27 IV-treated patients survived 2 years or more. It is concluded that for patients with hepatocellular carcinoma confined to the liver, the option of tumor resection either at the beginning of treatment or after chemotherapy offers the best chances for long-term survival. The overall prognosis is poor for patients with nonresectable hepatocellular carcinoma, but arterial infusion chemotherapy may double the median survival as compared to IV chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Effect of unlabelled monoclonal antibody (MoAb) on biodistribution of 111indium labelled (MoAb).

We have evaluated immunoscintigraphy in cancer patients using four 111In-labelled murine monoclonal antibodies (MoAb): 96.5 (anti-P97 of melanoma), ZME-018 (anti-high molecular weight antibody of melanoma), ZCE-025 (anti-CEA for colon cancer) and PAY-276 (anti-prostatic acid phosphatase for prostatic cancer). The effect of increasing the doses of unlabelled MoAb (co-infused with 1 mg labelled MoAb) on the relative body distribution of each labelled MoAb was assessed. Localization in the liver decreased significantly in all cases, with increasing MoAb dose, except for ZME-018. Localization in other organs increased significantly as the liver activity decreased. The spleen activity, however, fell in the case of MoAb ZME-018. Blood-pool activity increased with MoAb dose in all four MoAbs. These findings correlated with the rise in the detection rate of metastases, the plasma half-life, and other pharmacokinetic parameters. However, the dose level at which this correlation occurred varied with each antibody. These data demonstrate that co-infusion of unlabelled MoAb with 111In-labelled MoAb could alter the organ distribution, pharmacokinetics and tumour uptake in a favourable manner, though the degree to which this occurs depends on the antibody in question.

Antibodies, Monoclonal↗
PubMed1988

Improved tumor localization with increasing dose of indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer.

Monoclonal antibodies (MoAbs) against carcinoembryonic antigen (CEA) react with human colorectal cancer cells, and when labeled with a gamma-emitting radioisotope, may help to localize known and occult metastatic disease. We tested ZCE-025 (Hybritech, Inc, San Diego), a high-affinity immune gamma globulin1 (IgG1) MoAb anti-CEA that does not react with normal granulocyte glycoproteins in a phase I/II trial to determine the reagent's toxicity and its maximum efficacy in detecting metastatic colorectal cancer. Increasing doses of unlabeled ZCE-025 were mixed with 1 mg of Indium-111 (111In)-radiolabeled MoAb and administered intravenously (IV) to 34 patients who had metastatic colorectal cancer. Planar nuclear or single photon emission computed tomographic (SPECT) scans were performed 48 to 72 and 120 to 144 hours later. Total dose of MoAb and scanning sensitivity (number of imaged lesions/number of known lesions) were correlated up to 80 mg. At doses of 2.5 to 20 mg, a mean of 22% of the lesions were imaged; at 40 mg, 77% were imaged (P less than .01). Liver metastases were detected as areas of increased activity ("hot") at the 40 mg dose but showed decreased MoAb uptake at lower doses. At the 40 mg dose normal liver parenchymal uptake of the labeled MoAb was lower with respect to blood pool compared with the other doses. At 80 mg, however, sensitivity of detection declined to 21%. One milligram of 111In-labeled ZCE-025 antibody coinfused with 39 mg of unlabeled antibody appeared optimal for detecting metastatic colorectal cancer, particularly in the liver. Although the exact mechanism(s) for this dose effect is currently unknown, a partial "blocking" effect of unlabeled antibody with a change in MoAb biodistribution may be occurring.

Adult↗