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Biomedical subjects

D C Ihde

Publications and source records attributed to D C Ihde.

At least 73 records · Page 4Linked to original sources

Female patients with small cell lung cancer live longer than male patients.

PURPOSE: The incidence of lung cancer is rising in women in the United States, and recent reports have suggested that female patients treated for small cell lung cancer have an improved survival compared with their male counterparts. In view of these findings, we decided to determine if, in our patient population, women live longer than men and if a higher proportion of female patients are entering our trials. PATIENTS AND METHODS: The survival of women entering therapeutic clinical trials for small cell lung cancer from 1973 through 1986 at the National Cancer Institute-Navy Medical Oncology Branch was evaluated and compared with the survival of similarly treated men during the same time period. RESULTS: The survival of female patients was longer than that of male patients (median of 13 months versus 10 months). Cox proportional hazards modeling incorporating multiple prognostic factors indicated that women survived significantly longer than men (p = 0.002) when adjustment for other significant factors was made. This survival advantage for women was consistent in both early and late time periods analyzed. In addition, women constituted a larger proportion of patients entering clinical trials in the later time period, as is consistent with the rising incidence of lung cancer in women nationwide. CONCLUSION: We believe it will be important that comparisons of current clinical trials with older trials that enrolled fewer women control for the favorable prognostic factor of the female sex.

Carcinoma, Small Cell↗

Residual abdominal masses in aggressive non-Hodgkin's lymphoma after combination chemotherapy: significance and management.

When patients with aggressive lymphoma present with intraabdominal disease, a stable residual mass is frequently detected radiographically at the time of the clinical complete remission. To discern the optimal management for this clinical problem, we reviewed 241 patients with aggressive lymphoma treated at the National Cancer Institute (NCI) from 1977 to 1986. Seventy-two/241 patients (30%) had an abdominal mass at diagnosis and 29/72 (40%) were left with a radiographically detectable residual mass at clinical complete remission. The likelihood of a residual mass was much higher for patients with bulky disease (P2 less than .0003) (two-tailed test [P2]). Twenty-nine patients had radiologically stable residual masses after therapy, and of 22 (76%) with pathologic evaluations, 21 had negative specimens (95%) and one was positive (5%). None of the patients with negative pathologic evaluation has relapsed in the abdominal site (median follow-up, 31 months). Seven patients were observed clinically without laparotomy: five are alive, without evidence of disease, at 2 to 9 years; two relapsed with disseminated disease within 2 months of chemotherapy. Initial tumor size and size of the residual mass did not correlate with residual disease, since residual masses identified by radiographic examination did not usually harbor viable lymphoma cells. Aspiration cytology was negative for residual tumor in 15/16 cases. One negative result was not confirmed at laparotomy, presumably due to sampling error. The one positive aspiration was followed by a negative laparotomy, possibly due to subsequent tumor necrosis. Restaging laparotomy has a low yield. In most patients with aggressive lymphoma who have otherwise completely responded to carefully administered full-dose combination chemotherapy, stable residual abdominal masses can be closely followed clinically without surgical exploration.

Antineoplastic Combined Chemotherapy Protocols↗

A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.

Antineoplastic Combined Chemotherapy Protocols↗

The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment.

Patients with advanced indolent lymphoma often have long survival (median, 4 to 8 years) in spite of frequent relapses. The inability of combination chemotherapy or radiation therapy (RT) to render patients disease free has led to radically divergent treatment approaches. Initial treatment may vary from aggressive combined modality therapy to no initial treatment. We sought to evaluate these two divergent approaches in a randomized trial of advanced indolent lymphomas (nodular, poorly differentiated lymphocytic; nodular mixed; diffuse, well-differentiated lymphocytic; diffuse, intermediately differentiated lymphocytic; and diffuse, poorly differentiated lymphocytic). A total of 104 patients were entered: 44 were randomly assigned to "watch and wait" in which only carefully defined, limited RT was administered if necessary; 45 were randomly assigned to aggressive combined modality treatment with prednisone, methotrexate, doxorubicin, cyclophosphamide, plus etoposide plus mechlorethamine, vincristine, procarbazine, prednisone (ProMACE-MOPP), followed by total nodal irradiation (TNI); and 15, with symptoms requiring initial therapy, received the identical combined treatment but were not randomly assigned. Of 41 evaluable patients on watch and wait, 23 (56%) have still not required systemic therapy, although 16 (39%) have received limited RT. Median time to crossover was 34 months. Of 18 patients crossed over, seven of the 16 who completed therapy (43%) achieved CR; two (11%) have relapsed. Histologic progression was seen in six (15%) of 41 patients on watch and wait without intervening chemotherapy. Of 45 patients randomly assigned to chemotherapy, 37 (82%) have completed induction therapy, and 29 of the 37 (78%) achieved CR. Twenty-five of those 29 patients (86%) are still in their first remission. Median duration of initial remission has not been reached but will exceed 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Neoadjuvant chemotherapy for non-small cell lung cancer: current North American experience.

Recently, North American investigators have searched for effective chemotherapy or chemoradiotherapy regimens that can be employed before definitive surgery or radiation therapy in the treatment of stage III non-small cell lung cancer (NSCLC). Although these efforts have failed to identify a neoadjuvant regiment that clearly improves survival, the data from these trials do provide a direction for continuing research. It is now clear that the criteria for defining patients as operable, potentially operable, or inoperable have been heterogeneous and must be more carefully applied. With the current limited efficacy of chemotherapy in NSCLC, trials comparing different neoadjuvant regimens (chemotherapy, radiation therapy, and a combination of both), as well as comparative trials of definitive therapy with or without neoadjuvant therapy, will be required to clearly establish the role for neoadjuvant therapy in the treatment of this disease.

Carcinoma, Non-Small-Cell Lung↗

Paraneoplastic syndromes.

As the lengthy but nonetheless incomplete review suggests, paraneoplastic syndromes are protean in their manifestations and, for the most part, poorly understood. Indeed, some of the more common abnormalities in cancer patients that might be considered paraneoplastic--such as anorexia-cachexia syndrome or unexplained fever--have not been discussed because they are so poorly understood. Most of the syndromes reviewed are either clearly paraneoplastic or strongly associated with cancer. Their clinical importance does not lie in the number of patients affected; it is a small minority. Instead, the syndromes may occasionally be helpful in the diagnosis of cancer or in monitoring response to cancer therapy. They may also be confused with the effects of metastatic disease. In some patients, amelioration of the syndromes can reverse the patient's dominant symptoms and thus provide significant clinical palliation. In a more general context, studies of etiologic mechanisms in paraneoplastic syndromes may offer insights into a variety of unexplained abnormalities in cancer patients. The best-understood syndromes result from tumor production of biologically active substances or, to a lesser extent, from autoimmune phenomena. These would appear to be probable mechanisms in many recognized paraneoplastic syndromes of uncertain etiology and perhaps in some heretofore unrecognized paraneoplastic syndromes. Finally, paraneoplastic syndromes could also hold clues to the neoplastic process. Better understanding of the ways in which tumors regulate remote effects--such as release of TGFs--may ultimately enhance our knowledge of tumor growth itself.

Adrenocorticotropic Hormone↗

Recombinant interferon alfa-2a, an active agent in advanced cutaneous T-cell lymphomas.

The cutaneous T-cell lymphomas including mycosis fungoides and the Sézary syndrome, are indolent lymphomas with early systemic dissemination. Like the indolent B-cell lymphomas, they cannot be cured by currently available systemic chemotherapy so new systemic therapies need to be developed. A study of very high-dose recombinant interferon alfa-2a was, therefore, initiated in 20 patients with advanced cutaneous T-cell lymphoma (5 in stage II, 2 in stage III and 13 in stage IV). All patients were refractory to at least 2 standard therapies, including topical nitrogen mustard (18 patients), psoralens and ultraviolet A light (12 patients), total skin electron irradiation (14 patients) and systemic chemotherapy (16 patients). Nine out of 20 patients (45%; 95% confidence interval 25-69%) had either objective partial or complete responses within 3 months of starting treatment. Maximal response, however, often did not occur for at least one year. The median duration of response was 5.5 months and all complete responses lasted more than 2 years. Response frequencies were equal at both cutaneous and extracutaneous sites and in patients with or without prior chemotherapy. Toxicity was exhibited primarily as a flu-like syndrome consisting of fever, malaise, fatigue, anorexia and weight loss which necessitated dose reductions in all patients. Transient elevations in liver function and decreases in renal function and granulocyte counts occurred in some patients. It is concluded that interferon alfa-2a is highly active against advanced cutaneous T-cell lymphomas and that it should be studied in its early stages. It should also be evaluated in combination with other biological agents and with chemotherapy.

Acetaminophen↗

myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course.

44 small cell lung cancer cell lines established from 227 patients were studied for myc family DNA amplification (c-myc, N-myc, and L-myc). Two of 19 lines (11%) established from untreated patients' tumors had DNA amplification (one N-myc and one L-myc), compared with 11 of 25 (5 c-myc, 3 N-myc, and 3 L-myc) cell lines (44%) established from relapsed patients' tumors (P = 0.04). The 19 patients who had tumor cell lines established before chemotherapy treatment survived a median of 14 wk compared with 48 wk for the 123 extensive stage patients who did not have cell lines established (P less than 0.001). Relapsed patients whose cell lines had c-myc DNA amplification survived a shorter period (median of 33 wk) than patients whose cell lines did not have c-myc amplification (median of 53 wk; P = 0.04). We conclude that myc family DNA amplification is more common in tumor cell lines established from treated than untreated patients' tumors, and c-myc amplification in treated patients' tumor cell lines is associated with shortened survival.

Antineoplastic Combined Chemotherapy Protocols↗

Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis.

The clinical course of cutaneous T cell lymphoma (mycosis fungoides and Sezary syndrome) is generally indolent, but in occasional patients becomes fulminant. We found that biopsies from patients with accelerating disease can reveal cytologic transformation from previously observed small, convoluted lymphocytes to large cells that are similar to cells seen in large-cell lymphoma. The cerebriform nuclei characteristic of malignant T cells can only rarely be identified. Of 150 cutaneous T cell lymphoma patients we treated from 1976 to 1984, cytologic transformation was identified in 12 after review of peripheral blood smears and biopsies from skin, lymph nodes, and visceral sites. Patients who developed cytologic transformation were initially characterized by advanced stage (11 of 12), with lymph node effacement (seven of 11) and erythroderma (five of 12). The tumor cell DNA content after transformation was aneuploid (four of four), and the ability to form rosettes with sheep erythrocytes was retained in transformed cells (three of three). The median time from diagnosis of cutaneous T cell lymphoma to cytologic transformation was 21.5 months (range, 4 to 64), and the median survival from transformation was only 2 months (range, 0 to 19+). We conclude that cytologic transformation in cutaneous T cell lymphoma represents a distinct clinicopathologic entity, characterized by an aggressive clinical course.

Biopsy↗

The role of recombinant interferon alfa-2a in the therapy of cutaneous T-cell lymphomas.

Maximally tolerated doses of interferon alfa-2a, 50 X 10(6) U/m2 administered intramuscularly (IM) 3 times weekly, were given to 20 patients with advanced stages of cutaneous T-cell lymphoma (CTCL) to determine the efficacy and toxicity of this therapy. All patients were heavily pretreated and had failed standard therapies. Objective remissions were noted in 45% of the patients, including two patients who achieved complete remissions and seven patients who had partial remissions. The median duration of response was 5.5 months, with responses lasting a minimum of 3 months and a maximum of more than 3 years. Responses in excess of 2 years occurred in three of the nine responding patients. These results were achieved with moderate toxicities. The dose-limiting toxicity was a flu-like syndrome consisting of malaise, anorexia, weight loss, and falling performance status. Toxicity was observed in all patients but was always alleviated by dose reduction. Patients with indolent B-cell non-Hodgkin's lymphoma who received the same therapy had a similar objective response rate (54%) and showed the same toxicities. These trials were followed by an ongoing trial using the same dose of interferon in a different schedule given for 12 weeks followed by a dose escalation to 100 X 10(6) U/m2. Three partial responses were observed in the first 13 patients on this trial treatment. Other studies examining lower dose interferon compared to the 50 X 10(6) U/m2 are in progress. This study establishes interferon alfa-2a as a treatment of choice for patients with advanced cutaneous T-cell lymphomas refractory to chemotherapy and other standard therapies. Trials combining interferon with other standard treatments and the use of interferon in earlier stages of disease are needed.

B-Lymphocytes↗

Computed tomography of the abdomen and pelvis: documentation of tumor response and progression in disseminated prostate cancer.

Computed tomography of the abdomen and pelvis has been used to stage early prostatic cancer. We investigated its value in monitoring tumor response in more advanced disease. Serial computed tomography of the abdomen and pelvis was obtained along with multiple other staging tests prior to treatment and at 3- to 4-month intervals thereafter in 32 patients with stage D2 tumor treated initially with combination chemotherapy and with hormones at progression. Pretreatment lymphography with follow-up abdominal films was also performed. Initial computed tomography of the abdomen and pelvis showed evidence of node metastases in 35% of patients while lymphography was positive in 54%. Among 19 patients with tumor response and 25 with progression, the results of treatment were objectively documented by improvement or worsening, respectively, in a mean of 5.1 and 5.0 other staging tests, exclusive of computed tomography. Computed tomography of the abdomen and pelvis improved in 85% of responding patients examined. Progression was confirmed by worsening of computed tomography in 32%. Although lymphography was often abnormal prior to treatment, in our hands it was not useful in serial monitoring of tumor status. We conclude that serial computed tomography of the abdomen and pelvis, when initially positive, is a useful test to document objectively tumor response and progression in disseminated prostatic cancer.

Abdominal Neoplasms↗