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W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 73 records · Page 4Linked to original sources
PubMed1996

In vitro and in vivo studies of three radiolabelled somatostatin analogues: 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-D-Phe-1-OCT.

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues, 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2-2.0 nM) and low (Kd 5-15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using 123I-OCT and/or 123I-Tyr-3-OCT and/or 111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either 123I-OCT/123I-Tyr-3-OCT (four of five), 123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or 123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues: 123I-OCT, 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which 111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.

Adolescent↗
PubMed1996

123I-vasoactive intestinal peptide (VIP) receptor scanning: update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract.

Recent data suggest that functional receptors (R) for vasoactive intestinal peptide (VIP) are expressed on various tumor cells. The high-level expression of VIPR on tumor cells provided the basis for the successful use of 123I-labeled VIP for the in vivo localization of intestinal adenocarcinomas and endocrine tumors. We here report an update of our imaging results using 123I-VIP (150-200 MBg/1 microgram/patient) in 169 patients. In patients with pancreatic adenocarcinomas without liver metastases, the primary/recurrent tumor was visualized in 16 of 18 patients (89%) and liver metastases were imaged in 15 of 16 patients. In 11 of 12 patients with colorectal adenocarcinomas, the primary/recurrent tumor (92%) was imaged by 123I-VIP. Also, in 21 of 25 patients, liver metastases (84%); in 3 of 6 patients, lung metastases (50%); and in 4 of 5 patients, lymph-node metastases (80%) were imaged by 123I-VIP. In 10 of 10 patients with gastric adenocarcinomas, the primary/recurrent tumor; in 3 of 4 patients, liver metastases; and in 2 of 2 patients, lymph-node metastases were visualized by 123I-VIP. 123I-VIP localized primary intestinal carcinoid tumors in 15 of 17 patients (88%) and 8 of 10 primary insulinomas (80%). We conclude that the 123I-VIPR scintigraphy localizes intestinal adenocarcinomas and endocrine tumors as well as metastatic tumor sites.

Adenocarcinoma↗
PubMed1996

Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor.

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.

Adult↗
PubMed1996

Comparison of iodine-123-vasoactive intestinal peptide receptor scintigraphy and indium-111-CYT-103 immunoscintigraphy.

UNLABELLED: Recently, we have shown that the expression of receptors for vasoactive intestinal peptide (VIP) on intestinal adenocarcinomas can be used for in vivo targeting of primary or metastatic tumor sites using 123I-labeled VIP. Several other receptors and antigens including the TAG-72 protein have also been implemented for in vivo localization purposes. In this study, we have compared the in vitro and in vivo binding of 123I-VIP and of the 111In-labeled monoclonal antibody (MAb) directed against TAG-72 (OncoScint; 111In-CR-103) in patients with intestinal adenocarcinomas in a single-blinded, prospectively randomized trial. METHODS: Twenty patients were administered either 123I-VIP (150-200 MBq; 1 microgram) or 111In-CYT-103 (150 MBq; 1 mg) for one imaging study. After interim analysis demonstrated superior imaging with 123I-VIP, the next 10 patients (accounting for a total of 50 patients) enrolled in this trial underwent both studies in random order to allow for a direct comparison. RESULTS: In total, 123I-VIP scans were true-positive in 28 of 30 patients (93%) versus 17 of 30 patients administered 111In-CYT-103 (56%). In the subgroup of 10 patients enrolled in the second part of the study, primary intestinal adenocarcinomas were imaged in five of five patients with 123I-VIP and in only two of these patients with 111In-CYT-103. Liver metastases were visualized in five of six patients by 123I-VIP receptor scanning and in four of these patients with 111In-CYT-103. The in vitro results indicated significant binding of 123I-VIP to primary colorectal tumors as well as to HT29 and COLO320 adenocarcinoma cells. In vitro, adenocarcinoma cells also expressed abundant numbers of the TAG-72 antigen. CONCLUSION: Intestinal adenocarcinomas co-express VIP receptors and the IAG-72 antigen. Despite significant in vitro binding of both agents, however, the VIP receptor scan is more sensitive in localizing intestinal adenocarcinomas and metastatic spread.

Adenocarcinoma↗
PubMed1995

Phase I/II trial of dexverapamil, epirubicin, and granulocyte-macrophage-colony stimulating factor in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD) of a cytotoxic regimen consisting of the second-generation chemosensitizer dexverapamil (DVPM), high dose epirubicin, and recombinant human granulocyte-macrophage-colony stimulating factor (GM-CSF) in pancreatic carcinoma. PATIENTS AND METHODS: Twenty-eight previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were studied. Treatment consisted of oral DVPM at a dose of 1000-1200 mg/day for 3 days, epirubicin administered as an intravenous bolus injection on Day 2 with an initial dose of 90 mg/m2, and a dose of GM-CSF of 400 micrograms administered subcutaneously from Day 5s through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of four to eight patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. RESULTS: Hematologic toxicity, specifically granulocytopenia, constituted the dose-limiting toxicity with an MTD of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, four, two, and five patients experienced Grade 4 granulocytopenia during their first two treatment courses at levels 105, 120, and 135 mg/m2, respectively. Grade 4 granulocytopenia was observed in two, three, and one additional patients during subsequent courses with these levels. Nonhematologic toxicity was uncommon, generally modest, and did not correlate clearly with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Nine of 28 patients achieved partial responses to this therapy. Stable disease was observed in nine patients, and tumor progress occurred in 10. CONCLUSION: The MTD of epirubicin for this regimen with DVPM and GM-CSF was 120 mg/m2 every 3 weeks. Though it remains uncertain whether the encouraging response activity observed in this disease-oriented Phase I study was, in fact, due to successful modulation of multidrug resistance, these results suggest that this regimen is likely to be an effective and tolerable treatment strategy for patients with pancreatic cancer, which should be evaluated further.

Adenocarcinoma↗
PubMed1995

Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

A group of 28 previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were entered in this phase I/II study. Treatment consisted of oral dexverapamil 1000-1200 mg/day for 3 days, epirubicin given as an intravenous bolus injection on day 2 with a starting dose of 90 mg/m2, and 400 micrograms granulocyte/macrophage-colony-stimulating factor (GM-CSF) administered subcutaneously from day 5 through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of 4-8 patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. Haematological toxicity, specifically granulocytopenia constituted the dose-limiting toxicity with a maximum tolerated dose of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, 4, 2, and 5 patients experienced grade 4 granulocytopenia during their first two treatment courses at levels of 105, 120, and 135 mg/m2 respectively. Non-haematological toxicity was uncommon, generally modest, and did not demonstrate a clear relationship with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Of the 28 patients, 9 achieved partial reponses to this therapy. The recommended dose of epirubicin for this regimen with dexverapamil and GM-CSF is 120 mg/m2 every 3 weeks. Therapeutic results suggest this regimen to be an effective and tolerable treatment strategy in pancreatic cancer, which should be evaluated further.

Adenocarcinoma↗
PubMed1995

Treatment of advanced colorectal cancer with 5-fluorouracil and interferon-alpha: an overview of clinical trials.

5-Fluorouracil (5-FU) is the most active single agent for treatment of advanced colorectal cancer, although objective responses occur in only 20% of patients, and there seems to be no impact on overall survival. Experimental findings suggesting that interferon-alpha (IFN-alpha) enhances 5-FU cytotoxicity have stimulated an increasing number of clinical trials to evaluate the therapeutic potential of this combination. This article summarises the possible mechanisms of interaction of 5-FU and IFN-alpha, and provides an overview of the current status of this approach in advanced colorectal cancer. A computerised (Medline) and manual search were performed to identify all trials using 5-FU and IFN-alpha for the treatment of advanced colorectal cancer published in the English literature between 1960 and 1994. Information abstracted included treatment regimen, number of patients, pretreatment status, complete and partial remissions, remission duration, overall survival, and toxicity. A total of 417 patients were enrolled in 16 trials using different regimens of 5-FU and IFN-alpha, and double modulation of 5-FU with leucovorin (LV) and IFN-alpha was investigated in nine trials involving 332 patients. The mean overall response rate in these phase II trials was only 31% (range 3-76) and 35% (range 0-54), respectively. Early results of six prospectively randomised studies of 5-FU or 5-FU/LV +/- IFN-alpha also did not suggest a significant enhancement of the antitumour effectiveness with the addition of IFN-alpha. There is increasing evidence, however, that administration of IFN-alpha along with 5-FU enhances toxicity. Because of their modest therapeutic index, currently employed regimens of 5-FU +/- LV plus IFN-alpha cannot be recommended for routine use at the present time. The combination of 5-FU plus LV represents an equally effective and less expensive alternative. Nevertheless, there is still hope that further attempts to elucidate the complex mechanisms of this potentially synergistic drug combination will allow the rational design of regimens with a superior therapeutic index.

Clinical Trials, Phase II as Topic↗
PubMed1995

Combined intraperitoneal plus intravenous chemotherapy after curative resection for colonic adenocarcinoma.

Patients who underwent potential curative surgery for colonic adenocarcinoma were enrolled in a prospectively randomised, controlled clinical trial of combined intraperitoneal (i.p.) plus systemic intravenous (i.v.) chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant treatment approach, specifically addressing the risk of peritoneal and hepatic recurrence, could improve disease-free and overall survival. Between May 1988 and December 1990, 121 patients with resected stage III or high-risk stage II (T4N0M0) colon cancer were randomly assigned for observation (which was considered standard care until the NIH consensus conference) or adjuvant chemotherapy with LV (200 mg/m2) plus 5-FU (350 mg/m2), both given i.v. (days 1-4) and i.p. (days 1 and 3) every 4 weeks for a total of six courses. After a median follow-up time of 4.6 years, a comparative analysis between the two groups of patients suggested both an improvement in disease-free survival (75% versus 58%; P = 0.06) and a survival advantage (78% versus 63%; P = 0.05) in favour of adjuvant chemotherapy. The sites of recurrence were also different, i.e. local regional and intrahepatic tumour recurrences were observed in only 6/58 (10%) and 5/58 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%) observed patients. The overall benefit of adjuvant therapy appeared to be greatest in patients with stage III colon cancer. Treatment-associated toxicity was infrequent and generally mild with only 5% experiencing severe (WHO grade 3) adverse reactions. Interim results of this adjuvant trial suggest that combined i.p. plus systemic i.v. chemotherapy with 5-FU and LV represents a potentially effective adjuvant regimen in stage II/III colon cancer.

Adenocarcinoma↗
PubMed1995

Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours.

The new proliferation marker, tissue polypeptide-specific antigen (TPS), representing the specific epitope M3 of tissue polypeptide antigen, and three conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69 patients with advanced gastrointestinal tumours. The aim of our study was to assess the clinical relevance of these markers and to determine whether their use in monitoring the course of the disease can reduce the need for serial imaging procedures. At baseline, pathologically elevated TPS levels occurred in 90% of patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most sensitive marker in all three tumour types included in this analysis. Serial evaluations of TPS and other biochemical markers were available in 39 patients undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based regimen resulted in a partial response in 5/27 patients with colorectal cancer, whereas 2/12 patients with pancreatic cancer responded to therapy with a high-dose epirubicin combination regimen. All other patients had disease stabilisation or suffered from progressive disease. When compared with the results of serial CT scanning, the TPS correlated best with the course of the disease, the positive predictive value being 75% for a partial response, 96% for stable disease and partial response combined and 100% for progressive disease. The corresponding values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA-195. In summary, TPS seems to represent a sensitive, clinically relevant and specific marker of proliferative activity in gastrointestinal cancer. According to our preliminary results in colorectal and pancreatic cancer, TPS may be considered as the primary means of monitoring treatment, and imaging reduced to confirm the response.

Adult↗
PubMed1995

Vasoactive intestinal peptide receptor scintigraphy.

UNLABELLED: This study presents the biodistribution, safety and absorbed dose of 123I-VIP administered to 18 patients with intestinal adenocarcinomas or endocrine tumors. METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC. Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5 mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded during the initial 30 min. Thereafter, whole-body images were acquired in anterior and posterior views at various time points. Dosimetry calculations were performed on the basis of gamma camera data, urine, feces and blood activities. RESULTS: After injection of labeled peptide, the lung was the primary site of 123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4% 22 hr postinjection. Radioactivity was excreted into the urine and amounted to 37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16% within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248 mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104 muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi). CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and promising peptide tracer for localization of tumors expressing receptors for VIP.

Adenocarcinoma↗
PubMed1995

Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas.

UNLABELLED: Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and its diagnosis by conventional methods is still difficult. We hypothesized that the expression of specific receptors could possibly be used to improve in vivo localization of HCC with specific receptor-based radioligands. METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated. Scintigraphy was performed in 45 patients with histologically confirmed HCC using either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean. Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.

Aged↗
PubMed1995

Stereospecific pharmacokinetics of rac-5-methyltetrahydrofolic acid in patients with advanced colorectal cancer.

1. The pharmacokinetics and toxicity of racemic 5-methyltetrahydrofolic (rac-5-MTHF) acid after i.v. infusion were investigated in 18 patients with advanced colorectal cancer. Doses of 100-600 mg rac-5-MTHF/m2 were administered over 2 h together with a bolus of 500 mg/m2 5-fluorouracil (5-FU) as a midpoint injection. 2. The pharmacokinetics of both diastereoisomers were linear in the range from 100-600 mg 5-MTFH/m2. Independent of the administered dose, the maximal plasma concentration of [R]-5-MTHF was nearly twice that of [S]-5-MTHF. The elimination of [S]-5-MTHF from plasma was considerably faster than that of the [R]-isomer (elimination half-life: 3.1 +/- 1.0 h vs 8.3 +/- 3.2 h). No metabolites were detected in plasma and in urine samples. 3. The plasma protein binding was stereoselective ([R]-5-MTHF bound: 88.2 +/- 2.7%; [S]-5-MTHF bound: 59.9 +/- 6.8%; P < 0.001), causing a significantly higher renal clearance for [S]-5-MTHF when compared with the [R]-isomer (37.5 +/- 23.7 ml min-1 vs 12.7 +/- 11.2 ml min-1, P < 0.001). There was no dose dependence, but gender influenced renal clearance (CLren[R]-5-MTHF: male vs female: 20.5 +/- 14.5 ml min-1 vs 7.8 +/- 4.7 min-1, P = 0.03; CLren [S]-5-MTHF: male vs female: 57.2 +/- 21.7 ml min-1 vs 25.7 +/- 16.2 ml min-1, P = 0.006). 4. Toxic side effects of the combination 5-FU/5-MTHF were rare and generally mild, and included stomatitis, nausea/emesis, diarrhoea, anaemia, leukopenia, and thrombocytopenia. 5. In combination with 500 mg 5-FU/m2 a single dose of 600 mg rac-5-MTHF/m2 can safely be administered to patients with colorectal cancer. A similar therapeutic benefit of 5-MTHF to folinic acid in the biochemical modulation of 5-FU is supported by the comparison of in vitro and in vivo data.

Aged↗
PubMed1994

Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.

BACKGROUND: Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. METHODS: Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. RESULTS: Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors. CONCLUSIONS: Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Adenocarcinoma↗
PubMed1994

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.

BACKGROUND: Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression. RESULTS: The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Adult↗