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Biomedical subjects

D C Ihde

Publications and source records attributed to D C Ihde.

At least 37 records · Page 2Linked to original sources
PubMed1993

Individualized chemotherapy for patients with non-small cell lung cancer determined by prospective identification of neuroendocrine markers and in vitro drug sensitivity testing.

We attempted to prospectively select individualized chemotherapy for 165 non-small cell lung cancer patients based on in vitro analysis of neuroendocrine (NE) markers and drug sensitivity testing (DST) using fresh tumor. The chemotherapy used for small cell lung cancer (SCLC) was selected when NE marker expression determined by L-dopa decarboxylase assay was documented. Selection of chemotherapy for other patients was guided by DST results using a modified dye exclusion assay when available; otherwise etoposide and cisplatin was administered. A total of 112 of 165 (68%) specimens were assayed for L-dopa decarboxylase and 36 patients (22%) had DST. In vitro data directed management for 27 of 96 (28%) patients given chemotherapy: 6 with NE markers were treated with the SCLC regimen; and 21 (58% of those with DST) received their DST-selected chemotherapy regimen. There were no significant differences in response rate among all 3 treatment arms (P = 0.076). However, response to chemotherapy for the patients treated prospectively with a SCLC regimen was 3 of 6 (50%), marginally better than patients given their DST-selected chemotherapy regimen (2 of 21; 9%; P = 0.056) or those treated with etoposide and cisplatin (10 of 69; 14%; P = 0.061). When patients whose NE markers were identified retrospectively are included, 4 of 9 (44%) responded to administered chemotherapy, compared to 7 of 55 (13%) with no NE markers present (P = 0.04). There were no differences in survival among the three treatment groups. Cisplatin and etoposide comprised the most active regimen in vitro for tumors from 16 of 36 (44%) patients, potentially limiting the benefit of DST since this is often the empiric therapy for non-SCLC. Furthermore, the correlation between in vitro and clinical response is nonsignificant for all drugs tested, highlighting the overall relative resistance of non-SCLC tumors to currently available chemotherapy.

Antineoplastic Agents↗
PubMed1993

Smoking cessation after successful treatment of small-cell lung cancer is associated with fewer smoking-related second primary cancers.

OBJECTIVE: To determine the incidence of second primary cancers developing in patients surviving free of cancer for 2 or more years after treatment for small-cell lung cancer and to assess the potential effect of smoking cessation. DESIGN: Retrospective review of 540 patients from a single institution with a median follow-up of 6.1 years. SETTING: A single government institution (the National Cancer Institute). PATIENTS: Consecutive sample of 540 patients with histologically confirmed small-cell lung cancer treated from 1973 through 1989 on therapeutic clinical trials. MEASUREMENTS: The relative risk for second primary cancers and death were calculated in patients who remained free of cancer for 2 years after initiation of therapy. The relation of these end points to smoking history was also determined. RESULTS: Fifty-five patients (10%) were free of cancer 2 years after initiation of therapy. Eighteen of these patients developed one or more second primary cancers, including 13 who developed second primary non-small-cell lung cancer. The risk for any second primary cancer compared with that in the general population was increased four times (relative risk, 4.4; 95% CI, 2.5-7.2), with a relative risk of a second primary non-small-cell lung cancer of 16 (CI, 8.4-27). Forty-three patients discontinued smoking within 6 months of starting treatment for small-cell lung cancer, and 12 continued to smoke. In those who stopped smoking at time of diagnosis, the relative risk of a second lung cancer was 11 (CI, 4.4 to 23), whereas, in those who continued to smoke, it was 32 (CI, 12 to 69). CONCLUSIONS: Patients with small-cell lung cancer who survive cancer-free for more than 2 years have a significantly increased risk for development of a second primary smoking-related cancer. Cigarette smoking cessation after successful therapy is associated with a decrease in risk for a second smoking-related primary cancer.

Aged↗
PubMed1993

Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs.

OBJECTIVE: Design of a cost-effective algorithm for staging disease in patients with small-cell lung cancer. DESIGN: An algorithm was constructed by analyzing all permutations of a sequence of procedures required to stage disease in patients with small-cell lung cancer. Procedural costs were determined, and the model was applied to the small-cell lung cancer patient population treated at the National Cancer Institute, Bethesda, Md, from 1973 to 1989. The final algorithm was derived from the permutation with the lowest cost per accurately staged patient. SETTING: A single government institute, the National Cancer Institute. PATIENTS: Four hundred fifty-one patients with previously untreated, consecutive histologically documented small-cell lung cancer entered into therapeutic protocols at the National Cancer Institute from April 1973 through July 1989. Data were obtained from small-cell lung cancer protocol databases and patients' medical records. MAIN OUTCOME MEASURE: The cost per patient of each sequence of staging procedures when applied to the patient population. RESULTS: The least expensive sequence of procedures saved $1418 per patient when compared with application of a standard set of staging procedures to all patients. The major factor in reducing costs was the concept of stopping the staging procedures after a site of distant metastatic disease had been identified. CONCLUSIONS: An algorithm consisting of a set of sequential staging procedures can accurately stage disease in patients with small-cell lung cancer and save more than one third of the costs of an inclusive standard set of staging procedures.

Algorithms↗
PubMed1993

Atrial natriuretic factor and arginine vasopressin production in tumor cell lines from patients with lung cancer and their relationship to serum sodium.

Patients with lung cancer (n = 263) were studied to determine the relationship among ectopic production of atrial natriuretic factors (ANF) and arginine vasopressin (AVP), serum sodium, and patient outcome. Of 133, 21 (16%) patients with small cell lung cancer (SCLC) had hyponatremia (serum sodium, < 130 mmol/liter), compared to none of 130 (0%) patients with non-small cell lung cancer (P < 0.0001). Patients with extensive-stage SCLC and hyponatremia had shorter survival than patients with extensive stage SCLC and normal serum sodium values (P = 0.012). Of the 11 hyponatremic patients with SCLC and tumor cell lines available for study, 9 produced ANF mRNA, 7 of 11 produced AVP mRNA, and 5 of 11 produced both ANF mRNA and AVP mRNA. All 11 cell lines produced either ANF mRNA and ANF peptide or AVP mRNA and AVP peptide, or both. The quantity of AVP peptide in the tumor cell lines was more closely associated with hyponatremia in the patients (P = 0.0026, r2 = 0.28) than was the production of ANF peptide (P = 0.066, r2 = 0.12), although neither association was strong. All tumor cell lines studied from SCLC patients with hyponatremia produce ANF and/or AVP mRNA and peptides.

Arginine Vasopressin↗
PubMed1992

A meta-analysis of thoracic radiotherapy for small-cell lung cancer.

BACKGROUND: In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. METHODS: We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. RESULTS: The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined-therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/- SD) was 5.4 +/- 1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients: the relative risk of death in the combined-therapy as compared with the chemotherapy group ranged from 0.72 for patients less than 55 years old (95 percent confidence interval, 0.56 to 0.93) to 1.07 (0.70 to 1.64) for patients over 70. CONCLUSIONS: Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials.

Age Factors↗
PubMed1992

Prognostic implications of evaluation for lymph node involvement by T-cell antigen receptor gene rearrangement in mycosis fungoides.

We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were histologically uninvolved (LN1-2), dermatopathic nodes with clusters of atypical cells (LN3), and nodes effaced with lymphoma (LN4) and found TCRR in none of five LN1-2 nodes, 8 of 17 LN3 nodes, and 10 of 11 LN4 nodes. Further, the detection of TCRR correlated with presence of palpable adenopathy (P2 less than .0001) and was associated with a worse survival (P2 = .0024). Within the subgroup of patients with LN3 nodes, there was a trend (P2 = .14) toward inferior survival if nodes were involved by TCRR, irrespective of extent of skin disease. We conclude that detection of TCRR in nodes from mycosis fungoides patients is an objective and reliable means of assessing tumor infiltration of lymph node and is associated with an inferior survival.

Blotting, Southern↗
PubMed1992

Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.

Adult↗
PubMed1992

Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.

PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.

Adolescent↗
PubMed1992

The evolving role of systemic therapy in carcinoma of the lung.

Locally advanced lung cancer carries a poor prognosis, and its treatment continues to challenge medical, radiation, and surgical oncologists. While systemic chemotherapy has improved the survival of patients with small cell lung cancer (SCLC), the role and timing of thoracic radiotherapy has not been clearly defined. The roles of chemotherapy and radiotherapy appear to be reversed in the treatment of locally advanced non-small cell lung cancer (NSCLC). The routine use of thoracic radiotherapy has been shown to improve local control after surgery without affecting survival, due to a high incidence of distant metastases. This contrasts with the marginal survival benefit seen with chemotherapy in NSCLC. Nevertheless, the results of recent clinical trials in both SCLC and NSCLC are encouraging and support continued investigation. These studies and the results of recent pilot studies suggest that a closer integration of chemotherapy and radiotherapy (concomitant chemoradiotherapy) may be necessary for further improvement in outcome. This review will present the results of recent studies in systemic therapy of lung cancer and the evidence supporting concomitant chemoradiotherapeutic treatment of this disease.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Association between histological type and neuroendocrine differentiation on drug sensitivity of lung cancer cell lines.

Because most small-cell lung cancers (SCLC) are initially chemosensitive and express neuroendocrine (NE) cell markers and most non-SCLC tumors (NSCLC) are chemoresistant and do not express NE cell markers, we investigated the association between morphological type and NE cell differentiation with in vitro chemosensitivity. We tested a panel of 55 lung cancer cell lines established from previously untreated patients. These were tested against five cytotoxic drugs commonly used in the therapy of lung cancer, using the MTT assay. For comparative purposes, we also tested cell lines established from previously treated patients with SCLC and from colorectal tumors. The logarithms of the IC50 values of all of the cell lines were normally distributed, permitting the use of Student's t-test for assessment of differences. In general, the in vitro sensitivities of SCLC, NSCLC, and colorectal cell lines mirrored the clinical experience with these tumor types. Cell lines started from previously treated patients with SCLC were more resistant than those from previously untreated patients who responded to initial therapy. For all of the cell lines, the sensitivities to the five drugs tested were highly significantly correlated with each other. Thus, for comparative purposes, each group could be assigned an average standardized mean rank. About 15% of NSCLC tumors express multiple neuroendocrine (NE) cell markers and 4 of 5 lines from these NSCLC-NE tumors were relatively chemosensitive, similar to SCLC lines and significantly different from other NSCLC lines. Other NE cell lines tested included bronchial carcinoids and cell lines from small-cell carcinomas arising in extra-pulmonary locations (ExPuSC).(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

myc family DNA amplification in tumors and tumor cell lines from patients with small-cell lung cancer.

The myc family DNA copy number of 291 specimens (183 tumors and 108 tumor cell lines) from patients with small-cell lung cancer has been reported in 15 different studies. Thirty-five of 108 (32%) cell lines from small-cell lung cancer patients have myc family DNA amplification (16 c-myc, 7 N-myc, and 12 L-myc). Thirty-seven of 183 (20%) tumors from patients with small-cell lung cancer have myc family DNA amplification (3 c-myc, 13 N-myc, and 18 L-myc). The myc family DNA copy number in tumors from patients with small-cell lung cancer is similar in the majority of sites from the same patient. The presence of myc family DNA amplification in the tumor cell line is also typically present in the tumor from the same patient. myc family DNA amplification is present in a minority of patients with small-cell lung cancer, and the data on its association with shorter survival of patients are meager at present. Future studies on the biology of the myc family in small-cell lung cancer may require use of newer technologies that can work with small tissue samples typically available at the start of therapy.

Carcinoma, Small Cell↗
PubMed1991

myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens.

We studied 107 specimens (38 tumors and 69 tumor cell lines) from 90 patients with small cell lung cancer to determine the characteristics and clinical situations of patients from whom tumor cell lines could be established and the myc family DNA copy number. The proportion of extensive stage small cell lung cancer patients from whom a tumor cell line could be established prior to the initiation of therapy increased during the 10 years of the study (P less than 0.001). Amplification of one of the myc family genes occurred in 3 of 40 (8%) of the untreated patient specimens compared to 19 of 67 (28%) of the treated patient specimens (P = 0.01). The myc family DNA amplification occurred in 17 of 54 (31%) of the specimens from patients treated with cyclophosphamide-based combinations and 2 of 13 (15%) of the specimens from patients treated with etoposide/cisplatin (P = 0.25). Both tumors and tumor cell lines were obtained from 17 patients with small cell lung cancer and the myc family DNA copy number was similar in 16 of the 17 patients. We conclude that: (a) myc family DNA amplification occurs more commonly in specimens from treated than untreated patients (b) there are no prominent differences in the frequency of amplification following treatment with different chemotherapy regimens; and (c) myc family DNA amplification is similar in tumors and tumor cell lines from the same patients.

Antineoplastic Combined Chemotherapy Protocols↗