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Biomedical subjects

W K Hong

Publications and source records attributed to W K Hong.

At least 307 records · Page 17Linked to original sources
PubMed1992

The incidence of second primary tumors in long-term survivors of small-cell lung cancer.

PURPOSE AND METHODS: A review of 446 patients who were enrolled consecutively in small-cell lung cancer (SCLC) protocols was performed to identify in long-term survivors the frequency of new primary tumors and their clinical impact. RESULTS: Forty-seven patients (10.5%) were identified to be free of disease at 2 years. Second primary tumors (SPTs) were diagnosed in 14 patients. The overall risk for developing an SPT was 10.3% per person-year. Actuarial risk at 8 years was 50.3% for an SPT. CONCLUSIONS: In this review, SCLC showed one of the highest incidences of SPTs reported in aerodigestive tract malignancies. A long-term survivor was more likely to have an SPT than a relapse of SCLC. Consequently, the odds of death from an SPT compared with that from a relapse increased sharply from 1:13 within 4 years from diagnosis to 8:1 afterwards. Long-term survivors of SCLC would be excellent candidates for chemoprevention trials.

Adult↗
PubMed1992

Implantation metastasis of carcinoma after percutaneous fine-needle aspiration biopsy.

Implantation of malignant cells along the needle tract is an extremely rare but potential complication following percutaneous needle aspiration biopsy of malignant lesions. Percutaneous fine-needle aspiration biopsy (FNAB) has recently received more attention for cytologic diagnosis of bronchogenic carcinoma because of its high diagnostic yield, simplicity, and low morbidity. On the other hand, dissemination of cancer cells by needle aspiration biopsy can change a potentially resectable localized lung cancer to an unresectable one. We report two cases: one patient underwent FNAB of a metastatic left adrenal mass that seeded a paraspinal muscle implantation of malignant cells that subsequently developed a tumor mass, and the second patient had tumor cell implantation in the chest wall after FNAB of a pleural-based adenocarcinoma of the lung. The theoretical and practical importance of tumor cell spread along the needle tract is discussed. Because of its rare incidence, however, this complication should not affect the use of needle aspiration biopsy in bronchogenic carcinoma, although care should be undertaken during the procedure.

Adenocarcinoma↗
PubMed1992

Phase II study of cisplatin, ifosfamide with mesna, and etoposide (PIE) chemotherapy for advanced non-small cell lung cancer.

Ifosfamide has shown promising single-agent activity in non-small cell lung cancer (NSCLC). We combined ifosfamide (1,800 mg/m2 plus mesna 1,100 mg/m2 by intravenous [IV] continuous infusion daily for 3 days) with cisplatin (20 mg/m2 IV for 3 days) and etoposide (80 mg/m2 IV for 3 days) and treated 41 chemotherapy-naive patients with recurrent or metastatic NSCLC. Fifteen (40.5%) of the 37 evaluable patients had objective responses (1 complete and 14 partial). Patients with good performance status (Zubrod scale 0 or 1) had a higher response rate than the patients with poor performance status (Zubrod scale 2) (11 of 21 patients [52.4%] versus four of 16 [25.0%]), but the difference was not statistically significant (P = .09). Median survival has not been reached, with 17 patients still alive after a median follow-up of 39 weeks (range, 21 to 56). Significant myelosuppression occurred, with granulocytopenia being the dose-limiting toxicity. Overall, treatment was well tolerated. Considering the pooled response rate of 32% with cisplatin/etoposide regimens and the previous experience from our institution, the results with this three-drug regimen are very encouraging, and its further investigation is warranted.

Adenocarcinoma↗
PubMed1992

Phase II study of cisplatin, ifosfamide, and etoposide combination for advanced non-small cell lung cancer: final report.

Ifosfamide has shown promising single-agent activity in non-small cell lung cancer. We combined ifosfamide (1,800 mg/m2, plus 1,100 mg/m2 of mesna by intravenous continuous infusion daily for 3 days) with cisplatin (20 mg/m2 intravenously for 3 days) and etoposide (80 mg/m2 intravenously for 3 days) and treated 41 patients with recurrent or metastatic non-small cell lung cancer who had received no prior systemic chemotherapy. Fifteen (40.5%) of the 37 evaluable patients had objective responses (one complete and 14 partial). Patients with a good Zubrod performance status (ie, 0 or 1) had a higher response rate than those with poor performance status (ie, 2) (11 of 21 [52.4%] v 4 of 16 [25.0%]), but the difference was not statistically significant (P = .09). Median survival was 28 weeks for all patients and 59+ weeks for responders, with 11 patients still alive after a median follow-up of 59 weeks (range, 51 to 77 weeks). Overall, treatment was well tolerated, with granulocytopenia being the most frequent toxicity. Considering the pooled response rate of 32% with a cisplatin/etoposide regimen and the previous experience from our institution, the results with this three-drug regimen are encouraging, and its further investigation is warranted, particularly for patients who have good performance status and in a neoadjuvant setting.

Adult↗
PubMed1992

Current status of chemoprevention of head and neck cancer.

Chemoprevention involves efforts to block or reverse carcinogenesis before the development of invasive cancer. Natural agents, such as retinol and beta carotene, as well as synthetic retinoids have been studied as potential chemopreventive agents. In the head and neck, chemoprevention studies have included efforts both to reverse premalignant lesions such as oral leukoplakia and to prevent the development of second primary tumors. In one recent trial, high-dose 13-cis-retinoic acid treatment resulted in a dramatic reduction in the incidence of second primary tumors. However, significant toxicities were associated with the high dosage. This trial, as well as previous studies of oral leukoplakia, have led to the development of a chemoprevention trial using a low dose of 13-cis-retinoic acid to prevent second primary tumors following head and neck cancer. The rationale and design of this study are discussed in detail.

Head and Neck Neoplasms↗
PubMed1992

Suppression by retinoic acid of epidermal growth factor receptor autophosphorylation and glycosylation in cultured human head and neck squamous carcinoma cells.

The epidermal growth factor receptor (EGF-R) gene is overexpressed or amplified in various human squamous cell carcinomas, including those of the head and neck (HNSCC). Earlier we found that beta-all-trans-retinoic acid (RA) inhibited the growth and suppressed the aberrant squamous cell differentiation of several cultured HNSCC cell lines. Here we examined the effects of RA on the expression and function of EGF-R in two HNSCC cell lines, 1483 and 183, which exhibit distinct states of squamous cell differentiation, EGF-R mRNA levels, and responses to the growth inhibitory effects of RA. Treatment with RA (1 microM, 7 days) of the RA-sensitive 1483 cells decreased the level of EGF-R mRNA two- to four-fold and the binding of 125I-EGF to the cell surface by 30%-35%. In contrast, RA treatment of the 183 cells did not alter the EGF-R mRNA level or the binding of 125I-EGF. Other effects of RA on EGF-R structure and function were similar in both cell lines. RA did not alter the amount of immunoprecipitable [35S]methionine-labeled cellular EGF-R, 125I-cell surface labeled EGF-R, EGF-R internalization, or transforming growth factor alpha (TGF-alpha) mRNA. More important, RA treatment of both cell lines decreased EGF-R autophosphorylation activity detected in immune-complex-kinase assay by about three- and five-fold in the 1483 and 183 cells, respectively. Likewise, RA decreased the glycosylation of EGF-R in both cell lines. In the 1483 cells, RA suppressed the incorporation of either glucosamine or fucose by about 50%, whereas in the 183 cells RA suppressed the incorporation of fucose by about 80%. These results demonstrate that RA can modify the structure of the EGF-R by decreasing its glycosylation and suggest that these changes may suppress the autophosphorylation activity of the receptor kinase. The RA-induced changes in EGF-R do not correlate with the effect of RA on the growth of the cells but may be related to the suppression of squamous cell differentiation in the 1483 cells.

Carcinoma, Squamous Cell↗
PubMed1992

13-cis-retinoic acid and cancer chemoprevention.

Chemoprevention is the newest strategy for controlling and managing cancer. At present, the multistep character of epithelial carcinogenesis makes this disease process the most amendable to chemopreventive interventions, which occur in the postinitiation, preinvasive phases. Chemoprevention study has focused on oral carcinogenesis because of its excellent preclinical models, well-defined premalignant phase (leukoplakia), ease of monitoring, and link through field carcinogenesis to other epithelial carcinogeneses of the upper and lower aerodigestive tract. Retinoids, the derivatives of vitamin A, are the most-studied chemopreventive agents, and 13-cis-retinoic acid is the best-studied chemopreventive retinoid. Laboratory study of the newly discovered nuclear receptors of retinoic acid is closing in on the precise mechanism of retinoid action. Only 13-cis-retinoic acid, at high doses, has established chemopreventive activity, which is in suppressing oral premalignancy and preventing second primary head-and-neck tumors. Preclinical and clinical work in the other aerodigestive sites of the lung and esophagus are at an early phase of study with no conclusive results currently available. High-dose 13-cis-retinoic acid also has achieved significant activity in preventing invasive carcinomas of the skin. High-dose 13-cis-retinoic acid, however, is not ideal for widespread chemoprevention approaches because of its toxicity. The toxicity-to-risk balance is delicate and complicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal Neoplasms↗
PubMed1991

Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer.

The authors treated 32 patients with Stage IIIB or IV non-small cell lung cancer (NSCLC) with an outpatient regimen of edatrexate (10-ethyl-10-deaza-aminopterin) (10-EdAM) on days 1 and 8, cyclophosphamide on day 1, and cisplatin on day 1, repeated every 3 weeks with dose modification. The 22 men and 10 women (median age, 57 years of age) had no prior chemotherapy and a Zubrod performance status less than or equal to 2. A schedule with initial doses of 80 mg/m2, 800 mg/m2, and 80 mg/m2, respectively, yielded a 47% major response rate with two complete responses (95% confidence interval [CI], 25% to 70%), but it also yielded significant stomatitis and myelosuppression. A schedule with reduced starting doses (70 mg/m2, 700 mg/m2, and 70 mg/m2) was better tolerated, but dropped the major response rate to 27% with no complete responses (95% CI, 11% to 52%). Median survival time was 39 weeks for all 30 evaluable patients without a significant difference between the treatment groups (which were comparable in patient characteristics). Major response, however, was associated with longer survival time than minor response or no change (P = 0.024) or progressive disease (P = 0.001) (median survival times, 55, 39, and 27 weeks, respectively). When the doses delivered were compared, patients treated with the reduced dose schedule received less mean 10-EdAM per course (P = 0.01), although the doses of cyclophosphamide and cisplatin were comparable to the original dose schedule for the second course and thereafter. These results suggest that this three-drug regimen may have synergistic antitumor effects, with a steep dose-response relationship, particularly with 10-EdAM. With amelioration of the dose-limiting stomatitis of 10-EdAM, it seems possible to maximize the antitumor effects of this regimen.

Adult↗
PubMed1991

Clinical and immunomodulatory effects of combination immunotherapy with low-dose interleukin 2 and tumor necrosis factor alpha in patients with advanced non-small cell lung cancer: a phase I trial.

Sixteen patients with metastatic non-small cell lung cancer were treated with a combination of simultaneous low-dose interleukin 2 (IL-2) and tumor necrosis factor alpha. The purpose of this phase I dose escalation trial was to assess the clinical toxicities, immunomodulatory effects, and antitumor efficacy of this combination. Patients received a continuous daily i.v. infusion of 6 x 10(6) IU/m2 of IL-2 for 5 days and a concomitant daily i.m. dose of tumor necrosis factor alpha on each day of IL-2 administration. Tumor necrosis factor alpha administration started at a dose of 25 micrograms/m2/day (level I) for seven patients, 50 micrograms/m2/day (level II) for seven patients, and 100 micrograms/m2/day (level III) for two patients. Treatment was given at 3-week intervals. Only one patient required monitoring by an intensive care unit during therapy. Major toxic effects included fever, local skin reaction at the i.m. injection site, pancytopenia, and general malaise, all of which were reversible within 48 h of cessation of therapy. Dose level II was determined to be the maximum tolerated dose, with the dose-limiting toxicity being thrombocytopenia (less than 50,000/microliters). In 12 evaluable patients, one partial and three minor tumor regressions were observed. Seven patients with progressive disease before entry into this study had radiographic stabilization of their disease (median, 12 weeks) before termination of therapy due to progression. All patients exhibited biological responses including augmented lymphokine-activated killer and natural killer cell activities while receiving therapy, as assessed by the cytolysis of Raji- and K562 targets in vitro. Enhanced lysis of autologous tumor during therapy was demonstrated for four patients with available tumor samples. Serum levels of IL-2 were detected by enzyme-linked immunosorbent assay 2 weeks after cessation of therapy. This serum IL-2 had biological activity, which was evident from the ability to induce proliferation of NK-8 cells (an IL-2-dependent cell line) which was abrogated by anti-IL-2 antibody.

Adolescent↗
PubMed1991

Retinoic acid suppression of squamous differentiation in human head-and-neck squamous carcinoma cells.

Retinoids (vitamin A analogues) inhibit the squamous differentiation of normal and malignant epithelial cells. This study investigated the ability of the head-and-neck squamous-cell carcinoma (HNSCC) cell line 1483 to undergo squamous differentiation in the absence and presence of beta-all-trans retinoic acid (RA). The growth of these cells in culture is accompanied by an increase in keratinocyte transglutaminase, involucrin and keratin KI, 3 established markers of squamous cell differentiation. Higher levels of these differentiation markers were detected in cells cultured in delipidized serum (DLS), from which endogenous retinoids have been extracted, than in cells cultured in fetal bovine serum (FBS), which contains retinoids. Treatment with I microM RA decreased the levels of the various differentiation markers in cells cultured in either FBS or DLS as revealed by immunofluorescent labelling of permeabilized cells and by immunoblotting of cell extracts using specific monoclonal or polyclonal antibodies. The cells' ability to cross-link proteins to form envelopes under the plasma membrane was stimulated in the presence of calcium ionophore but inhibited by RA. These results indicate that the malignant 1,483 HNSCC cells recapitulate the main characteristics of normal squamous-cell differentiation in culture and that RA suppresses this differentiation as it does in normal keratinizing epithelial cells.

Calcium↗
PubMed1991

Expression of blood-group antigen A--a favorable prognostic factor in non-small-cell lung cancer.

BACKGROUND: New prognostic factors are needed to guide the treatment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression. METHODS: The presence of blood-group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 164 patients who underwent curative surgery for non-small-cell lung cancer from 1980 through 1982. Monoclonal antibodies were used to detect the A and B antigens, and Ulex europaeus agglutinin I to detect H antigen. RESULTS: Survival of the 28 patients with blood type A or AB who had primary tumors negative for blood-group antigen A was significantly shorter than that of the 43 patients with antigen A-positive tumors (P less than 0.001) and of the 93 patients with blood type B or O (P = 0.002). The respective median survival times were 15, 71, and 39 months. Disease progressed significantly earlier in the 28 patients with tumors negative for blood-group antigen A than in the antigen A-positive patients (P less than 0.001). Expression of blood-group antigen B or H in tumor cells did not correlate with survival. Cox proportional-hazards regression analysis showed that expression of blood-group antigen A in tumor cells added significantly to the prediction of overall survival provided by other known prognostic factors among the patients with blood type A or AB (P = 0.004). CONCLUSIONS: Expression of blood-group antigen A in tumor cells is an important favorable prognostic factor in patients with non-small-cell lung cancer. This variable needs to be considered in the design of future trials of therapy.

ABO Blood-Group System↗
PubMed1991

Phase II clinical trial of 4'-O-tetrahydropyranyl-adriamycin (THP-adriamycin) in recurrent squamous cell carcinoma of the head and neck.

Fourteen patients previously treated with surgery, radiotherapy, and/or chemotherapy for primary squamous cell carcinoma of the head and neck were treated with 4'-O-tetrahydropyranyl-Adriamycin (THP-adriamycin) for locally or distantly recurrent disease. The starting dose was 60 mg/m2 by i.v. infusion, with courses repeated every 3 to 4 weeks. A total of 34 courses of treatment were delivered (median, 2; range, 1-6). All patients were evaluable for response and toxicity. There were no responses. Severe (grade 3 or 4) neutropenia occurred in 11 patients. Thrombocytopenia, anemia, and gastrointestinal toxicity were modest, and no hepatic, renal, or cardiac toxicity was observed. The lack of response in association with severe neutropenia and moderate other toxicities using this dose and schedule of THP-Adriamycin should be taken into consideration prior to the pursuit of further study of this compound in a similar patient population.

Adult↗
PubMed1991

Alleviation by leucovorin of the dose-limiting toxicity of edatrexate: potential for improved therapeutic efficacy.

Edatrexate (10-ethyl-10-deaza-aminopterin; CGP 30 694) is a methotrexate (MTX) analogue that shows promise against non-small-cell lung cancer (NSCLC) and other tumors. Since edatrexate's mechanism of action is the same as that of MTX, we used leucovorin in an attempt to alleviate its dose-limiting toxicity, stomatitis. In four patients with NSCLC who had experienced significant stomatitis after treatment with edatrexate, cyclophosphamide, and cisplatin, we observed a remarkable reduction in stomatitis following the administration of low-dose leucovorin. On the basis of the results obtained in these individuals, we treated 15 additional patients with this three-drug regimen plus leucovorin rescue. These subjects could tolerate the treatment with lesser degrees of stomatitis and received higher edatrexate doses in subsequent courses as compared with the patients who previously received this regimen without leucovorin rescue. This approach is expected to improve the therapeutic indices of edatrexate and edatrexate-containing chemotherapy regimens by modifying the dose-limiting toxicity of this antineoplastic agent.

Aminopterin↗
PubMed1991

Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting.

Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.

Adult↗
PubMed1991

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.

Aged↗