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Biomedical subjects

C S Portlock

Publications and source records attributed to C S Portlock.

At least 37 records · Page 2Linked to original sources
PubMed1991

High-dose cisplatin plus dacarbazine in the treatment of metastatic melanoma.

The combination of cisplatin plus dacarbazine (DTIC) is active in metastatic melanoma with response rates reported between 10% and 55%. To optimize this regimen, a Phase II study was conducted employing a dose intensity of cisplatin higher than previously reported. Twenty-two patients were treated. Eight patients received cisplatin 100 mg/m2 on days 1 and 8 combined with DTIC 300 mg/m2 on days 1, 2, 8 and 9 (regimen A). Because of excessive toxicity, the protocol was modified so that cisplatin was given at 50 mg/m2 per day and DTIC 350 mg/m2 per day on days 1 through 3 (regimen B). The overall response rate was 32% and consisted of four partial and three complete responses (CR). The median duration of response was 6 months. Two of the CR remain in sustained, unmaintained remission in excess of 1.5 years. All seven patients that responded were treated on regimen B. High-dose cisplatin plus DTIC on a 3-day schedule represents an effective, well-tolerated therapy for metastatic melanoma.

Adult↗
PubMed1990

Mediastinal irradiation in combined modality therapy for Hodgkin's disease.

Patients with Hodgkin's disease who present with large mediastinal masses in the setting of either early or advanced stage disease are frequently treated with combined modality therapy. Policies for radiation dose to the mediastinum in these settings range from no radiation to doses in the 3600-4000 cGy range. We reviewed the charts of 50 patients treated with radiation therapy following remission induction with chemotherapy between 1979 and 1983 to determine whether the dose of radiation to the mediastinum could be correlated with mediastinal control, relapse-free, and overall survival. Patients were divided into groups with small (SM, 30 pts.) and large (LM, 20 pts.) mediastinal masses and analyzed according to whether they had received low dose (LD, less than or equal to 2500 cGy) or high dose (HD, greater than 2500 cGy) radiation to the mediastinum. The 5-year relapse-free survival (RFS) for all 50 patients was 84% (+/- 8%, 95% confidence limits). For the patients with small mediastinal masses, 5-year RFS was 81% +/- 20%, and for the patients with large mediastinal masses, 89% +/- 16%. No clear dose-response effect was observed when the outcomes of the low dose and high dose patients were compared. This was true even in the patients with large mediastinal masses although the high dose subset of this group included patients felt to be at a higher risk for relapse following chemotherapy. Nine of eleven patients with large mediastinal masses treated with chemotherapy and low dose radiation remain disease-free. There was only one isolated mediastinal relapse in the entire group of patients. Treatment was well tolerated with no acute treatment-related deaths. Two patients developed second malignancies. We conclude that combined modality therapy using low dose radiation results in excellent 5-year relapse-free survival for most small and many large mediastinal mass patients, and that it is not necessary to treat all chemotherapy patients who present with mediastinal disease with high dose radiation to achieve these relapse-free survival rates.

Adult↗
PubMed1987

High-dose pulse chlorambucil in advanced, low-grade non-Hodgkin's lymphoma.

High-dose pulse chlorambucil was given orally at a dose of 16 mg/m2 daily for 5 consecutive days each month, as reported by Cadman et al. It was used to treat 33 patients with advanced, low-grade non-Hodgkin's lymphoma. With median follow-up of 4.2+ years, 70% of the patients achieved objective response. Eleven of 24 patients with follicular small cleaved cell lymphoma (FSCL) had pathological complete response; nine of 24 with FSCL and three of seven with small lymphocytic lymphoma had partial response. Median disease-free survival was 28 months. Actuarial survival for all patients was 60% at 5 years from initiation of therapy. Treatment toxicity was minimal. Pulse chlorambucil is an effective and minimally toxic palliative therapy for advanced FSCL.

Administration, Oral↗
PubMed1986

Prognostic indicators in diffuse large-cell (histiocytic) lymphoma.

Identification of prognostic groups among patients with diffuse large-cell (histiocytic) lymphoma (DHL) would help to select specific therapy for individual patients and allow comparisons among combination chemotherapy clinical trials. The Ann Arbor staging system is of limited value in predicting outcome in diffuse histiocytic lymphoma. Prognostic factors have been examined by various groups without a consensus of reliable prognostic indicators. This study was undertaken to examine the validity of a predictive model for response to treatment and survival in DHL. Eighty-six patients with the diagnosis of DHL treated with combination chemotherapy between the years 1976 and 1982 were examined for prognostic variables influencing response to treatment and survival. The variables examined included: age, sex, presence or absence of systemic symptoms, serum lactic dehydrogenase (LDH), sites of disease involvement, bulk of disease, prior therapy, stage of disease, according to the Ann Arbor classification, and pathological criteria, according to the Lukes Collins classification. Factors achieving a p-value in the 0 to 0.05 range with univariate analysis for predicting response were age and systemic symptoms. Factors significant for overall survival were age and bone marrow involvement. These factors have been found to influence survival in previous studies, but there has not been a consistency regarding the importance of these factors. Large numbers of patients must be examined for various factors in order to allow identification of prognostic groups among patients with DHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.

Actuarial Analysis↗
PubMed1986

Therapeutic approaches to the treatment of hairy cell leukemia.

Although a rare disease, hairy cell leukemia has great biologic and clinical significance. New therapeutic options of alpha-interferon and pentostatin have challenged the role of splenectomy in the overall management of the disease. alpha-Interferon can now be considered the treatment of choice for patients who progress after splenectomy, and it may also be considered as initial treatment in selected patients. Future clinical trials will focus on the relative efficacies of alpha-interferon and pentostatin, their potential for sequential or combined use, and the role of splenectomy.

Antineoplastic Agents↗
PubMed1984

Adriamycin (doxorubicin), vinblastine, and mitomycin C combination chemotherapy in refractory breast carcinoma.

Twenty-seven evaluable patients with refractory, metastatic breast carcinoma were treated with Adriamycin (doxorubicin) 30 mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 28 every 8 weeks, and mitomycin C 10 mg/m2 intravenously on day 1 every 8 weeks (AVM). There were three complete and six partial responses for a total response rate of 33%. In addition, 2 patients had minimal responses, and 10 patients achieved disease stabilization. Median time to disease progression for responders was 116 days (range, 49-812+ days). Drug toxicity was tolerable: 12 patients (44%) experienced significant bone marrow suppression. There were no drug-related deaths. Although AVM appears to be an active drug combination in heavily pretreated patients with metastatic breast carcinoma, the contribution of vinblastine and mitomycin C to single agent Adriamycin in previously treated patients is not clear from this study.

Adult↗
PubMed1984

Hodgkin's disease.

The outlook for patients with Hodgkin's disease has improved dramatically over the past 20 years. The question is no longer whether cure is possible, but rather, how can cure be best achieved. With better understanding of the biology of Hodgkin's disease and with continued evolution of treatment approaches, the goal of curing all patients with Hodgkin's disease is clearly within reach. This article provides a summary of current concepts in the biology and management of Hodgkin's disease. Staging, treatment options, and complications of therapy are discussed.

Adolescent↗
PubMed1984

Resistance to methotrexate due to gene amplification in a patient with acute leukemia.

A patient is described with acute myelocytic leukemia refractory to conventional therapy, who also became highly resistant to methotrexate (MTX) after repeated courses of this drug. Leukemia cells from this patient were found to contain an elevated level of dihydrofolate reductase (DHFR) activity, with no change in the affinity of the enzyme for MTX. A sensitive "dot blot" assay revealed a fourfold increase in the gene copy number of DHFR. Southern blot analysis with a human DHFR cDNA probe confirmed this increase in the gene copy number, and demonstrated a similar restriction pattern with Eco R1, Hind III, and Pst 1 as seen with a highly amplified human leukemia cell line, K562. Additional DHFR fragments were detected, not seen in the K562 blot, suggesting the presence of pseudogenes, or a result of gene rearrangements occurring as part of the amplification process. Resistance to MTX in this patient was therefore ascribed to gene amplification and overproduction of DHFR.

Adult↗
PubMed1981

Extralymphatic Hodgkin's disease. Prognosis and response to therapy.

Three hundred eighteen patients with pathologic stage IA and IB, IIA and IIB, and IIIA Hodgkin's disease who entered into Stanford University Medical Center randomized trials comparing radiation therapy alone to radiation therapy plus six cycles of adjuvant chemotherapy were evaluated. Of these, 54 patients had extralymphatic (E) lesions. There were five relapses among these patients (9 percent), not different from the 37 relapses among the remaining 264 patients (14 percent) with Hodgkin's disease confined to the lymphatic system. Actuarial survival and freedom from relapse were not significantly different for patients with or without extralymphatic disease. The survival of patients with extralymphatic disease was similar whether they received radiation therapy alone or radiation therapy plus chemotherapy.

Antineoplastic Agents↗