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Biomedical subjects

L Leong

Publications and source records attributed to L Leong.

At least 55 records · Page 3Linked to original sources
PubMed1995

Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels.

The purpose of this study was to estimate the response rate, response duration, and survival of patients with advanced ovarian cancer treated with a 132-hr continuous infusion of high-dose calcium leucovorin in combination with five consecutive daily bolus doses of 5-fluorouracil (5-FU) and to correlate changes in CA-125 levels with clinical and radiologic assessment of disease progression. Forty-six heavily pretreated patients [median number of previous chemotherapy regimens, 2.5 (range 1-7)] with advanced ovarian cancer received 132-hr continuous infusions of calcium leucovorin (500 mg/m2/day) for 5 1/2 days, with daily bolus doses of 5-FU (370 mg/m2/day) for 5 days beginning 24 hr after initiation of the calcium leucovorin. Twenty-three patients had clinically measurable disease and 23 had evaluable disease; CA-125 levels were performed prior to each treatment course and after the final course of therapy. One of 42 patients had a partial response to combination chemotherapy (duration, 8.9 months); 16/42 had stable disease [median duration, 4.9 months (range, 2.4-9.0 months)]. Toxicity of combination therapy included mild myelosuppression and stomatitis, similar to previously reported toxicity profiles for the 5-FU and calcium leucovorin combinations. Sensitivity of CA-125 levels as a single indicator of disease progression was 55%. The combination of infusional high-dose calcium leucovorin and 5-FU has little activity in refractory ovarian cancer. CA-125 levels incorrectly predict clinical disease activity in about one-third of cases and should not be the sole criterion for determination of clinical response when evaluating chemotherapeutic efficacy in heavily pretreated patients.

Adenocarcinoma↗
PubMed1995

Mitomycin C and menadione for the treatment of lung cancer: a phase II trial.

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.

Adult↗
PubMed1995

Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Adult↗
PubMed1995

Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.

PURPOSE: To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS: Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS: Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION: CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.

Adult↗
PubMed1995

Integrin signaling: roles for the cytoplasmic tails of alpha IIb beta 3 in the tyrosine phosphorylation of pp125FAK.

pp125FAK (focal adhesion kinase) a protein tyrosine kinase that may mediate cellular responses to adhesion, is activated and tyrosine-phosphorylated when platelets adhere to fibrinogen via the integrin, alpha IIb beta 3. To determine whether either of the cytoplasmic tails of alpha IIb beta 3 regulates FAK phosphorylation, CHO cells were stably transfected with alpha IIb beta 3 or various cytoplasmic tail truncation mutants. Cells expressing wild-type alpha IIb beta 3 or alpha IIb beta 3 that lacked the COOH-terminal 13 or 18 residues of the 20 residue alpha IIb tail adhered to and spread on fibrinogen or on an anti-alpha IIb antibody, and FAK became tyrosine-phosphorylated. FAK also became phosphorylated in adherent cells lacking the COOH-terminal 35 or 39 residues of the 47 residue beta 3 tail, although the extent of phosphorylation was reduced by about 50% in the latter mutant. Little or no FAK phosphorylation was observed if 46 residues were deleted from the beta 3 tail. None of these beta 3 truncation mutants spread on the anti-alpha IIb antibody. When cells with wild-type alpha IIb beta 3 or truncated beta 3 were detached from a surface, FAK became rapidly dephosphorylated. In contrast, FAK remained phosphorylated in the two alpha IIb truncation mutants for up to 90 minutes in suspension. This persistent phosphorylation was not due to occupancy of alpha IIb beta 3 by adhesive ligands because it was also observed with an alpha IIb tail truncation mutant that contained an additional mutation in the extracellular portion of the receptor that prevents ligand binding. These studies demonstrate that: (1) the beta 3 cytoplasmic tail, including the membrane-proximal portion, is involved in initiation of FAK phosphorylation; (2) FAK phosphorylation can be initiated by cell adhesion in the absence of cell spreading; and (3) the membrane-distal portion of the alpha IIb cytoplasmic tail may normally function to dampen FAK phosphorylation in non-anchored cells.

Amino Acid Sequence↗
PubMed1995

5-Fluorouracil and high-dose calcium leucovorin for hepatocellular carcinoma: a phase II trial.

A phase II trial of 5-fluorouracil (5-FU) [250-450 mg/m2/day x 5 days as an intravenous (IV) bolus] combined with calcium leucovorin (500 mg/m2/day x 5 1/2 days by continuous IV infusion) administered on a 28-day schedule was performed in 15 patients with advanced hepatocellular carcinoma. The median age was 58 years; performance status ranged from 50 to 100%. Of 15 evaluable patients, 1 (7%) had a partial response lasting 2.4 months; 8 (53%) had stable disease with a median duration of 5.7 months; and 6 (40%) had progressive disease with a median time to progression of 2.7 months. Median survival was 3.8 months. Treatment with 5-FU and calcium leucovorin was moderately well tolerated; 9% of the treatment courses were complicated by grade 3 or 4 hematological toxicity, and 10% of the courses were complicated by grade 3 or 4 gastrointestinal toxicity. Despite the efficacy of the combination of 5-FU and leucovorin in advanced colorectal cancer, our results document the general resistance of hepatocellular carcinoma to modulated 5-FU.

Adult↗
PubMed1995

Inhibition of growth of human ovarian cancer in nude mice by luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75).

OBJECTIVE: To report on the in vitro and in vivo inhibitory effects of LH-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75; Asta Medica, Frankfurt-Main, Germany) against a panel of human ovarian carcinomas. INTERVENTIONS IN VITRO STUDIES: the effect of SB-75 was measured using a standardized chemosensitivity assay in the following ovarian cancer cell lines: UCI 101; UCI 107; PA-1; NIH: OVCAR 3; UCLA: 222; A2780, parental; A2780-CR, cisplatin resistant; A2780-DR, doxorubicin resistant; and the human breast cancer cell line, MCF-7. Results were expressed as percent growth inhibition determined by crystal violet photometric analysis. In vivo studies: the antiproliferative effect of this agent was examined using UCI-107, a primary epithelial ovarian carcinoma cell line, in a nude mouse model. On day 0, 10 x 10(6) UCI 107 cells were implanted subcutaneously into 20 intact female athymic nude mice (5 to 6 weeks old). On day 8, the mice were randomly divided into two groups of 10; control mice were implanted with miniosmotic pumps filled with a vehicle solution consisting of 5.2% mannitol in saline; and treated animals received pumps filled to deliver continuous administration of SB-75 at 60 micrograms per mouse per day. RESULTS IN VITRO STUDIES: direct inhibition of cell proliferation by SB-75 was not observed at concentrations ranging from 1 nM to 100 microM (exposure lasting three to four cell doublings) with the exception of MCF-7, which demonstrated a 33% inhibition at the latter concentration. In vivo studies: on day 16, caliper measurements were taken from subcutaneous tumor nodules in SB-75-treated and untreated mice and a significant difference of 270% in mean tumor volume was observed. End point was determined, on day 30, when control tumor volume approached 10,000 mm3. At that time the difference in mean tumor volumes increased to 600%, indicating a substantial antiproliferative effect had been achieved in the SB-75-treated group. CONCLUSION: Our in vitro findings show direct inhibition by SB-75 on proliferation of human breast cancer cells. This direct inhibition in vitro was not observed in our ovarian cancer cell lines. However, in vivo SB-75 caused a significant inhibition of growth of human epithelial ovarian cancer. This may be a result of inhibition of the pituitary gonadal axis and gonadotropin secretion. Our results warrant further investigation.

Animals↗
PubMed1994

alpha-Thrombin-induced human platelet activation results solely from formation of a specific enzyme-substrate complex.

Prior studies using the mutant thrombin, thrombin Quick I, indicate that this protease induces maximum platelet aggregation and intraplatelet [Ca2+] fluxes at agonist concentrations where dissociable, equilibrium platelet binding is undetectable and led to the conclusion that thrombin interaction with its platelet "receptor" is best described kinetically by formation of an enzyme-substrate complex. This conclusion was substantiated further in the present studies by demonstrating that both thrombin Quick I and thrombin mimicked the thrombin receptor agonist peptide in the induction of the platelet activation-dependent events required for functional Prothrombinase assembly and that a rabbit antibody raised against KATNATLDPRSFLLR, a pentadecapeptide which represents amino acids 32-46 in the platelet thrombin receptor/substrate and spans the thrombin cleavage site, inhibited both thrombin- and thrombin Quick I-induced platelet activation responses equivalently. The antipeptide antibody had a more pronounced inhibitory effect on the rate of the thrombin-induced response rather than the magnitude of the response suggesting competition for the cleavage site, consistent with the observation that pretreatment of metabolically-inhibited platelets with thrombin, which was removed by washing, eliminated specific antibody binding due to removal and/or masking of antibody epitopes. Concentrations of the antipeptide antibody that inhibited thrombin- and thrombin Quick I-induced increases in intracellular [Ca2+] flux by as much as 97% did not alter the dissociable equilibrium binding of 125-I-FPR-thrombin to platelets. These combined data indicate that the hydrolytic event initiated by thrombin or thrombin Quick I interaction with the platelet receptor/substrate for thrombin is unrelated to the dissociable equilibrium binding of thrombin to membrane sites described previously by classical receptor-ligand binding analyses.

Amino Acid Sequence↗
PubMed1994

Limitations of transvaginal sonography and color Doppler imaging in the differentiation of endometrial carcinoma from benign lesions.

We conducted this study to test the hypothesis that transvaginal ultrasonography and color Doppler imaging of the uterine arteries are complementary methods in the assessment of patients with postmenopausal bleeding. Sixty-seven patients were studied. Seventeen suffered from endometrial carcinoma, 12 from benign endometrial lesions (six polyp, six hyperplasia) and 38 had no organic pathology. Transvaginal ultrasonography was found to be superior to CDI in the detection of pathologic conditions of the endometrium, but neither method can distinguish benign lesions from their malignant counterparts. CDI does not give additional information over that obtained by transvaginal ultrasonography in the assessment of patients with postmenopausal bleeding, and the limitations of both methods in the differentiation of endometrial carcinoma from benign lesions need to be recognized.

Arteries↗
PubMed1994

Ultrasound guided transperineal prostatic aspiration biopsy: experience in Hong Kong.

OBJECTIVE: The purpose of this study is to correlate the result of the ultrasound guided transperineal aspiration biopsy with the clinical findings. MATERIALS AND METHODS: We retrospectively studied 27 patients who had been subjected to ultrasound guided transperineal prostatic aspiration biopsy in our institution during the period 1990 to 1992. The patients were divided into two groups: Group A--those with clinically palpable nodules on digital examination, and Group B--those without palpable nodule but with clinical evidence of prostatic enlargement and/or bladder outlet obstruction. RESULTS: There were 8 biopsy proven cancers, 4 of them were palpable lesions while the other 4 were clinically non-palpable. The overall positive predictive value was 29.6%; this increased to 40% if the lesions were palpable but decreased to 23.5% if the lesions were non-palpable. CONCLUSION: The overall positive predictive value of this technique was found to be consistent with other studies using different methods of biopsies. The positive predictive value was increased if the abnormality was clinically palpable. This technique was also found to be safe and no significant complication was observed in these patients.

Aged↗
PubMed1993

Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma.

PURPOSE: To study the role of computed tomography in the pre-therapy evaluation of nasopharyngeal carcinoma. METHODS AND MATERIALS: The computed tomography of 119 new patients of nasopharyngeal carcinoma were evaluated independent of clinical findings for neck node metastases, and then compared with clinical findings. Contrast enhanced axial scans were obtained at 5 mm intervals with the infraorbitomeatal line parallel to the gantry. Scans were obtained from the supra-sellar cistern to the C5 or C6 vertebra for the evaluation of the base of skull, nasopharynx, paranasopharyngeal space and the upper and mid neck. RESULT: The present study confirmed the disparity of nodal extent documented by clinical palpation and computed tomography. Of the 37 patients who have no clinically palpable node (N0), computed tomography showed nodal involvement in 11 (29.7%) of them, and they were up-staged from N0 to N1. Computed tomography showed multiple or bilateral nodes in seven (58.3%) of the 12 patients with AJC N1 disease and they were hence up-staged to N2. All together, there were 28 (23.5%) patients who have no computed tomography evidence of nodal involvement by tumor. In agreement with clinical experience, the most commonly involved nodal groups were the upper internal jugular and upper spinoaccessary, followed by the lateral retropharyngeal. The percentage of nodes which were not clinically palpable was roughly the same for different regions (15-30%), except, as expected, that all the retropharyngeal nodes were not palpable. The risk of harboring retropharyngeal node was proportional to the size of the largest node in the ipsilateral neck. CONCLUSION: A significant proportion of patients with clinically negative neck (N0) or AJC N1 disease will be upstaged by computed tomography, thus supporting its routine use in pre-therapy evaluation of nasopharyngeal carcinoma.

Head and Neck Neoplasms↗
PubMed1993

Carcinoma of the anus treated with primary radiation therapy and chemotherapy.

Between 1983 to 1989, 24 patients with previously untreated carcinoma of the anal canal (less than 3 centimeters in five patients and more than 3 centimeters in 19 patients) were entered in a prospective nonrandomized protocol of primary radiotherapy (4,050-4,500 cGy days one to 28) and chemotherapy (10 milligrams per meter squared of mitomycin C, on day two and 1,000 milligrams of 5-fluorouracil per molar squared for days two to five and 28 to 32). Therapy was discontinued for two patients because of severe (grade 4) skin reactions. The remaining patients tolerated the regimen well, with the exception of two patients who had grade 3 hematologic toxicity and three patients with grade 3 to 4 complications of the gastrointestinal tract. All of the patients who completed the regimen had a complete clinical and pathologic response when restaged six weeks after completion of therapy. All patients with lesions of less than 3 centimeters and 13 of 19 patients with lesions greater than 3 centimeters have remained free of disease (median follow-up period of 41 months; median survival rate of 36 months). Before 1983, 19 patients underwent abdominal perineal resection as primary treatment for carcinoma of the anus. Only six of seven patients with lesions less than 3 centimeters and zero of the 12 patients with lesions equal or greater than 3 centimeters have remained alive and free of disease. Eighteen of 24 patients treated with chemotherapy and radiotherapy only have remained free of disease and have preserved anal function. These results are superior to those reported with primary surgical treatment and primary radiotherapy only.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The thrombin high-affinity binding site on platelets is a negative regulator of thrombin-induced platelet activation. Structure-function studies using two mutant thrombins, Quick I and Quick II.

To elucidate the thrombin domains required for high-affinity binding and platelet activation, the platelet binding properties of thrombin and two mutant thrombins, thrombin Quick I and Quick II, were compared to their agonist effects in elevating intraplatelet [Ca2+]. In Quick I, a mutation within the fibrinogen binding groove results in decreased clotting and platelet aggregating activities, whereas in Quick II, a mutation in the primary substrate binding pocket abolishes both activities. Dysthrombin binding was decreased compared to thrombin. The fibrinogen binding groove appeared more important than the primary substrate pocket for high-affinity binding since Quick I showed drastically reduced, and Quick II only slightly reduced, binding affinity (Kd approximately 200 and approximately 10 nM, respectively). The deduced interaction of thrombin with its high-affinity binding site indicated that the thrombin catalytic site is directed toward the platelet surface and therefore, when bound, is proteolytically inactive. Quick I (0.5-5 nM) elicited intraplatelet [Ca2+] fluxes at concentrations where high-affinity binding was undetectable. Saturation of high-affinity binding sites with active-site-modified thrombin did not affect thrombin-induced (0.5 nM) or Quick I-induced (5 nM) responses. In contrast, addition of D-Phe-Pro-Arg chloromethyl ketone (FPRCK) subsequent to thrombin or Quick I stimulation of platelets abolished agonist-induced responses. Since Quick I was only 10-17% as effective as thrombin in increasing intraplatelet [Ca2+], our data support a model in which thrombin acts enzymatically on a platelet membrane "substrate", through an interaction mediated in part by the fibrinogen binding groove of thrombin. This conclusion is consistent with the inhibition observed with high concentrations (greater than 100 nM) of Quick II and FPRCK-modified thrombin (FPR-thrombin) in platelets stimulated with low concentrations of thrombin (less than 0.5 nM) or Quick I (less than 2 nM), consistent with inhibition by substrate depletion. In contrast, concentrations of FPR-thrombin or Quick II (less than 100 nM), which saturated predominantly the high-affinity binding sites, enhanced the platelet responses induced by thrombin (less than 0.5 nM). Thus, occupation of the high-affinity sites with inactive thrombin increased the concentration of active thrombin available for substrate interaction. Quick I-induced responses were not enhanced, consistent with its inability to interact with the high-affinity site. Since thrombin bound to the high-affinity site is proteolytically inactive, we hypothesize that the thrombin high-affinity binding site on platelets functions to alter thrombin activity and platelet activation.

Amino Acid Chloromethyl Ketones↗
PubMed1992

Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer.

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.

Aged↗
PubMed1991

Cranial nerve involvement and base of the skull erosion in nasopharyngeal carcinoma.

In a prospective study of 262 consecutive patients with nasopharyngeal carcinoma (NPC), using computed tomography (CT) as their baseline evaluation, erosion of the base of the skull and intracranial extension into the middle cranial fossa were found in 31.3% and 12.2% of patients, respectively. Thirty-four of these patients had cranial nerve involvement at presentation; 30 of them had involvement of one or more of the third to sixth cranial nerves. Most cases of intracranial extension of tumor were accompanied by erosion of the base of the skull, but the reverse was not true. All patients with cranial nerve palsy involving the third to sixth cranial nerves had associated erosion of the ipsilateral base of the skull. The CT evaluation of patients with cranial nerve involvement who are believed to harbor NPC should include thin cuts of the base of the skull for detection of subtle bone erosion. This may be the only clue to the presence of a small NPC. The prognostic significance of cranial nerve involvement, base of the skull erosion, and intracranial extension of the tumor on the survival of the group of 84 patients who had T4 tumors was evaluated with regression analysis using the Cox model. Only cranial nerve involvement was found to be a significant factor influencing survival.

Cranial Nerve Neoplasms↗
PubMed1991

Phase II study of 4'-deoxydoxorubicin (esorubicin) in advanced or metastatic adenocarcinoma of the stomach.

4'-deoxydoxorubicin (DxDx) was administered to 17 patients with locally advanced or metastatic gastric adenocarcinoma. Treatment cycles were repeated every 21 days. 15 eligible patients with a Karnofsky performance status of 50% or better (median: 70%) received at least one course of treatment; a median of 2 courses of DxDx was delivered (range 1 to 13). The median dose per treatment course was 26 mg/m2 (range 8.5 mg/m2 to 53 mg/m2). 69% of patients required dose reduction following the first course of therapy due to grade 3 or 4 myelosuppression, primarily neutropenia. The principal side effects included anemia, mild gastrointestinal toxicities, and alopecia; one patient experienced a 10% decrease in cardiac ejection fraction without clinical cardiac toxicity. Of the 15 patients assessable for response and toxicities, 1 patient had a partial response lasting 2.5 months. The median survival from the time of the first treatment was 3.3 months. We conclude that DxDx has only limited activity in the treatment of advanced gastric adenocarcinoma.

Adenocarcinoma↗