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Biomedical subjects

S R Veach

Publications and source records attributed to S R Veach.

15 recordsLinked to original sources
PubMed1994

Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer.

The use of mitomycin for metastatic colorectal cancer has been limited by mitomycin's myelosuppressive potential. The objective of this randomized study was to determine whether WR-2721 would decrease the hematologic toxicity of mitomycin in patients with colorectal cancer resistant to fluorouracil-based therapy. Ninety-seven patients with refractory colorectal cancer were randomized to receive either mitomycin 20 mg/m2 only or the same dose of mitomycin after pretreatment with WR-2721, 910 mg/m2. The principal toxicity in both groups was thrombocytopenia. The platelet nadirs were lower in patients receiving single-agent mitomycin (P = 0.026). Surprisingly, no clinical complete or partial responses were noted in either group, and survival was not different between the two groups. Thus, while WR-2721 decreased the thrombocytopenia associated with mitomycin therapy, mitomycin was ineffective in the treatment of refractory colorectal carcinoma.

Adult↗
PubMed1990

A phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity.

A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20% activity (95% confidence intervals 0-19%) in NSCLC and an 11% response rate in SCLC (95% confidence intervals 2-34%). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.

Adult↗
PubMed1990

Phase II trial of intermittent high-dose recombinant interferon alfa-2a in mycosis fungoides and the Sézary syndrome.

We previously demonstrated that recombinant interferon alfa-2a (IFN-alfa) in a dose of 50 X 10(6) U million units (MU)/m2 intramuscularly (IM) three times per week has efficacy against mycosis fungoides (MF) and the Sézary syndrome (SS). However, this regimen given to patients with refractory disease was uniformly complicated by toxicities requiring major dose reductions. The present study was designed to determine if intermittent high-dose IFN-alfa would preserve efficacy and decrease toxicity in a similar patient population. Twenty-four patients with advanced disease refractory to one or more standard therapies received IFN-alfa, 10 MU/m2 IM on day 1 followed by 50 MU/m2 IM on days 2 to 5 every 3 weeks; after the first four cycles, stable and partially responding patients underwent dose escalation to twice the starting dose. One complete (CR) and six partial responses (PRs) were observed (response rate, 29%; 95% confidence interval, 13% to 51%) lasting 4 to 19 months (median, 8 months). No improvement in objective response was seen in the eight patients who received dose escalation. Dose reductions were necessary in eight of 22 patients receiving one or more cycles of therapy. Weighted mean dose rate intensity for patients on this study over the first four cycles of treatment was 65.5 MU/m2/wk compared with 73.2 MU/m2/wk over the first 12 weeks of treatment in patients from the previous study, in which all 19 patients receiving more than 1 week of treatment required dose reduction. IFN-alfa is effective against previously treated MF and the SS and is better tolerated on this intermittent schedule.

Combined Modality Therapy↗
PubMed1988

Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups.

STUDY OBJECTIVE: To determine the optimal staging evaluation at the time of initial diagnosis of mycosis fungoides or the Sézary syndrome. DESIGN: Retrospective review of a uniformly staged inception cohort. SETTING: Single-institution tertiary care center. PATIENTS: 152 consecutive patients who had mycosis fungoides with or without the Sézary syndrome within 6 months of the initial definitive diagnosis. INTERVENTION: A detailed staging evaluation including physical examination, routine laboratory studies, chest roentgenogram, lymphangiogram, peripheral blood smear, lymph node biopsy, bone marrow aspirate or biopsy, and liver biopsy in selected patients. MEASUREMENTS AND MAIN RESULTS: Univariate adverse prognostic features at initial diagnosis in patients with mycosis fungoides included (P less than 0.01) one or more cutaneous tumors or generalized erythroderma, adenopathy, blood smear involvement with Sézary cells, lymph node effacement, eosinophilia, and visceral involvement. Important, independent prognostic factors in a multivariate analysis are the presence of visceral disease and type of skin involvement. CONCLUSIONS: A staging system based on histopathologic evaluation of skin, lymph nodes, blood, and visceral sites provides more comprehensive prognostic information than clinical evaluation of skin disease and adenopathy. Patients may be divided at initial presentation into three prognostic groups: good-risk patients, who have plaque-only skin disease without lymph node, blood, or visceral involvement (median survival, greater than 12 years); intermediate-risk patients, who have cutaneous tumors, erythroderma, or plaque disease with node or blood involvement but no visceral disease or node effacement (median survival, 5 years); and poor-risk patients, who have visceral involvement or node effacement (median survival, 2.5 years).

Actuarial Analysis↗
PubMed1988

The development of small cell lung cancer in the contralateral lung of a patient surviving 8 years after the original diagnosis of small cell lung cancer.

The development of non-small cell lung cancer in patients successfully treated for small cell lung cancer has been previously described. Many of these non-small cell tumors appear to be second primary lung tumors. However, the development of second primary small cell lung cancers has not been clearly delineated. In this report, a patient with limited stage small cell lung cancer who had a complete response to chemotherapy plus chest radiotherapy and remained cancer-free for 8 years is described. Small cell lung cancer developed in this patient's contralateral lung with no evidence of recurrence at the original primary site. Clinical evidence suggests that a second primary small cell lung cancer developed in this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

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↗
PubMed1987

Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial.

STUDY OBJECTIVE: To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. DESIGN: Randomized trial with a median follow-up of 57 months. SETTING: A single government institution--the National Cancer Institute. PATIENTS: Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. INTERVENTIONS: Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. MEASUREMENTS AND MAIN RESULTS: The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p less than 0.001), and significantly longer survival (p less than 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. CONCLUSION: A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.

Actuarial Analysis↗
PubMed1986

Late intensive combined modality therapy followed by autologous bone marrow infusion in extensive-stage small-cell lung cancer.

To attempt to improve the poor prognosis of extensive-stage small-cell lung cancer (SCLC) patients, we tried to administer late intensive combined modality therapy (LICMRX) to patients with good tumor regression after 12 weeks of conventional chemotherapy. Twenty-nine consecutive extensive-stage SCLC patients received 6 weeks of cyclophosphamide, methotrexate, and lomustine (CMC) induction therapy, followed by 6 weeks of vincristine, doxorubicin, and procarbazine (VAP). After restaging for assessment of tumor response, autologous bone marrow (ABM) was collected in patients in good medical condition with complete response (CR) or partial response (PR) and no tumor on marrow examination. LICMRX consisted of irradiation with 2,000 rad in five fractions for five days to sites of initial tumor involvement, followed by cyclophosphamide, 60 mg/kg for 2 days, and etoposide, 200 mg/m2 for 3 days and then by ABM infusion. Prophylactic cranial irradiation (PCI) was administered thereafter, but no further chemotherapy was used. Due to lack of tumor regression or poor medical condition, only ten of the original 29 patients were eligible for LICMRX; two refused, so only eight (28%) received therapy. Three patients who began LICMRX in CR developed recurrence of SCLC after an additional 4, 8, and 15 months. Of five patients with PR, one attained CR but relapsed at 3 months, two remained in PR and progressed at 2 and 4 months, and two died of infection without recovery from LICMRX. Mean time from ABM infusion to recovery of granulocyte count to 500/microL was 15.8 days in the six surviving patients (range, 12-22). The major non-hematologic toxicity of LICMRX was severe esophagitis. Among all 29 patients, there were six CRs (21%) and no 2-year survivors, compared with a CR rate of 36% and 10% 2-year survivors in 78 extensive-stage patients previously treated with CMC plus VAP without LICMRX. We conclude that the LICMRX given in this study can be administered to only a minority of extensive-stage SCLC patients and is very unlikely to yield substantial improvement in the fraction of 2-year survivors (95% confidence limits for 2-year survival 0% to 10%).

Adult↗
PubMed1986

Etoposide (VP-16) and cisplatin in previously treated small-cell lung cancer: clinical trial and in vitro correlates.

Treatment of patients with relapsed small-cell lung cancer (SCLC) has been uniformly unsuccessful. Recently, the combination of etoposide (VP-16) and cisplatin in this setting has been reported to result in up to 50% response rates. We treated 29 patients with relapsed SCLC with this combination and found only a 12% response rate. The discrepancy between our results and those of others is most likely due to differences in prior treatment of the patients, although the effect of dose and schedule modifications are considered. Our patients had received a six-drug regimen over a median of 7 months and had a median drug-free interval before this treatment of only 3 weeks. Evidence is presented that suggests that this aggressive initial therapy affected both host tolerance to further treatment and the development of tumor resistance at the cellular level.

Adult↗
PubMed1984

Pulmonary blastoma. Case report and literature review of chemotherapy experience.

Pulmonary blastoma is a rare primary lung neoplasm, occurring in both children and adults, which is pathologically, clinically, and prognostically distinct from other lung tumors. Usually it has been treated with surgery, but both chemotherapy and radiotherapy have been used for metastatic disease, and in the adjuvant setting. A patient is described who presented with metastatic pulmonary blastoma. Treatment with cyclophosphamide, vincristine, doxorubicin, and dactinomycin resulted in an objective response as judged by standard criteria. The literature is reviewed for other experience with chemotherapy in this rare lung tumor. This four-drug combination appears to show promise for tumor response, and is deserving of further trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Recombinant leukocyte A interferon: an active agent in advanced cutaneous T-cell lymphomas.

High-dose recombinant leukocyte A interferon (50 X 10(6) U/m2 body surface area, intramuscularly, three times weekly) was tested in a clinical trial involving patients with advanced cutaneous T-cell lymphomas to determine its effectiveness and toxicity. All 20 patients had advanced stages of disease refractory to two or more standard therapies. Objective partial remissions lasting 3 months to more than 25 months (median, 5 months) were documented in 9 patients. The major dose-limiting toxicity was a severe influenza-like syndrome with malaise, anorexia, depression, weight loss, and decreased performance status; this effect was reversible after dose reductions in all patients and did not recur with re-escalation of doses in 10 patients. This interferon preparation is highly effective in the treatment of advanced refractory cutaneous T-cell lymphomas, and new schedules to reduce toxicity and achieve complete responses, combined treatment with chemotherapy or serotherapy, and its use in earlier stages of disease should be investigated.

Adult↗
PubMed1983

Small-cell carcinoma of lung: reinduction therapy after late relapse.

Some patients with small-cell carcinoma of lung can be expected to achieve long-term disease-free survival. However, relapses may occur even after 2 years. Information on the treatment of these patients is sparse, although response rates to "salvage" therapy in patients with progressive disease while receiving treatment are poor. We report six patients who had relapses after more than 2 years in complete remission. Five patients were retreated with chemotherapy including some or all of the drugs in the initial treatment, and four had responses with a median duration of 10 months (range, 2 to 18 months). Thus retreatment with chemotherapy similar to the initial treatment can occasionally achieve second responses persisting up to 1 year or longer. The high incidence of patients who have relapses after 2 years confirms previous data on relatively slow growth rates in small-cell carcinoma.

Adult↗
PubMed1980

Krukenberg carcinoma of the ovary with bone marrow involvement. Report of 2 cases and review of the literature.

Krukenberg carcinoma of the ovary accounts for 1 to 3% of ovarian neoplasms. The nature and behavior of this particularly virulent tumor remain unclear. In this paper, 2 cases are presented of Krukenberg carcinoma metastatic from the gastrointestinal tract; in both bone marrow involvement was detected early in the course of the disease. The histopathology of the tumor is described. A comprehensive review of the literature in English is provided, and therapeutic approaches to the disease are discussed.

Adult↗
PubMedDate not supplied

Metastasizing auricular basal cell carcinoma.

Basal cell carcinoma represents the most common skin cancer and involves the head and neck area in 80% to 85% of all patients treated. Despite their frequent occurrence, metastatic spread from these tumors is rare. This paper presents a case of a patient who had a metastasizing basal cell carcinoma. Despite control of primary disease by radical surgery and adjunctive irradiation, bony metastasis was found within nine months of therapy. Palliative therapy was given, but the patient died five months later. The pathophysiology of the metastasizing basal cell carcinomas is described, and a rationale for therapy presented.

Bone Neoplasms↗