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Biomedical subjects

S P Hubbard

Publications and source records attributed to S P Hubbard.

10 recordsLinked to original sources

Prolonged disease-free survival in Hodgkin's disease with MOPP reinduction after first relapse.

Thirty-two patients with Hodgkin's disease who relapsed after a first complete remission induced by nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) were retreated with MOPP chemotherapy. Nineteen patients achieved a second complete remission. Median duration of the second complete remission was 21 months. The likelihood of achieving a second complete response could be predicted by the duration of the first response. Fourteen of 15 patients whose first complete remission was longer than 12 months achieved a second complete response in contrast to five of 17 patients whose initial complete remission lasted less than 12 months (P less than 0.001). Median survival of all patients in this study who were re-treated with MOPP was longer than 4 years after their first relapse. We conclude that patients with Hodgkin's disease who relapse after a first complete remission induced by MOPP are not necessarily resistant to further MOPP therapy and can achieve long-term survival with MOPP reinduction.

Adolescent

Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P less than 0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma.

Adenocarcinoma

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma.

The results of clinical and surgical staging in a series of 170 patients with non-Hodgkin's lymphoma are reviewed. Advanced disease (Stage IV) was established without laparotomy in 95 patients (56%), primarily through bone marrow biopsy, closed liver biopsy, and peritoneoscopy. Laparotomy revealed a high incidence of liver involvement and involvement of lymph nodes outside of conventional abdominal irradiation portals only in patients with nodular types of pathology and in patients with positive lymphangiograms. The limitations and indications for staging laparotomy are discussed in the context of these findings.

Biopsy

Peritoneoscopy: a technique to evaluate therapeutic efficacy in non-Hodgkin's lymphoma patients.

Peritoneoscopy was performed in 22 patients with non-Hodgkin's lymphoma as a re-staging technique to rule out relapse or persistence of active disease after intensive chemotherapy and/or radiotherapy. Fifteen patients with previous hepatic involvement achieved a complete clinical remission; however, five patients (33%) had persistent disease proved by biopsy at peritoneoscopy. In seven patients suspected to have a clinical relapse, peritoneoscopy biopsies documented relapse in three patients (43%), including two patients with negative percutaneous liver biopsies. Because of its low morbidity rate (4%), peritoneoscopy can be utilized to re-stage hepatic involvement by non-Hodgkin's lymphoma patients more accurately than percutaneous liver biopsies and with less morbidity than laparotomy.

Humans

Sequential staging in non-Hodgkin's lymphoma.

The results of staging in 170 patients with non-Hodgkin's lymphoma have been reviewed; all patients were subjected to a series of sequential procedures, including lymphangiography, bone marrow biopsy, and liver biopsy (performed percutaneously, by peritoneoscopy, or by laparotomy). A high incidence of involvement of bone marrow, liver, and abdominal nodes was found in patients with nodular types of lymphoma and in those with diffuse lymphocytic lymphoma, with less than or equal to 20% remaining in stage I or II at the completion of staging in each of these subgroups. Only in patients with histiocytic lymphoma was there an appreciable percentage (31%) remaining in the stage I-II categories after staging. In this study, 75 patients remained in stage III or less after completing the non-surgical phase of staging, and laparotomy was utilized in only 50 patients (30%). At laparotomy, involvement of the liver or the mesenteric or portal lymph nodes was found in 81% of patients with a positive lymphangiogram but in only 18% of those with a negative lymphangiogram.

Biopsy

A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors.

Polyriboinosinic-polyribocytidylic acid (poly I - poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis. Forty-four separate drug trials were comprised of various schedules and routes of administration. Toxic reactions included fever (in 66% of the trials), transient elevation of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase (25%), minimal laboratory evidence of coagulation abnormalities (59%), and hypersensitivity (5%). These toxic manifestations did not relate to dose level or magnitude of interferon induction. Poly I - poly C administered iv induced low serum concentrations of interferon in 24/38 trials (63%), but the correlation between drug dose and peak interferon titer was not linear. Poly I - poly C administered iv or im was not effective as an inducer of interferon in the cerebrospinal fluid. Similarly, poly I - poly C administered im or by inhalation did not produce detectable serum levels of interferon. No patients experienced an objective tumor response to the administration of poly I - poly C, and most (76%) had progression of their disease while receiving the drug.

Acute Disease

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma.

The yield of specific diagnostic procedures in the staging of non-Hodgkin's lymphoma was assessed in 170 consecutive patients who were evaluated with a sequence of diagnostic procedures. Stage III or Stage IV disease was established in 141 of 170 patients (80%) by nonsurgical procedures, including lymphangiography (positive in 78%), bone-marrow biopsy (positive in 39%), percutaneous liver biopsy (positive in 21%), and peritoneoscopy-directed liver biopsy (positive in 29% of those tested). Staging laparotomy showed disease outside conventional nodal irradiation fields in 21 of 26 patients with a positive lymphangiogram, but in only three of 17 patients with a negative lymphangiogram. The yield of staging procedures was highest in patients with nodular lymphomas, only 6% of whom were Stage I or Stage II after staging, but was lowest in patients with histiocytic lymphoma, 30% of whom had localized disease. This study shows that the presence of disseminated disease can be detected in the majority of patients with non-Hodgkin's lymphoma without the use of staging laparotomy.

Adult

Advanced diffuse histiocytic lymphoma, a potentially curable disease.

Twenty-seven patients with advanced diffuse histiocytic lymphoma (reticulum-cell sarcoma) were treated with combination chemotherapy utilising nitrogen mustard (or cyclophosphamide), procarbazine, vincristine, and prednisone. Elven (41%) achieved a complete remission and only one of these has had a recurrence of tumour. The remaining ten complete responders were free of all evidence of tumour when last seen 26-105 months from the end of treatment. In contrast, all non-responders or partial responders have died. An interpretation of published survival data suggests that this virulent disease evolves quickly and is usally rapidly fatal if treatment is unsuccessful. Survival free of disease beyond 2 years from the end of treatment may be considered tantamount to cure. This definition of cure, previously applied only to patients treated with radiotherapy, seems applicable to patients who acheive complete remissions with modern drug treatment.

Administration, Oral

Preliminary Results of trials of chemotherapy in advanced ovarian carcinoma.

A search for improved forms of systemic chemotherapy in advanced ovarian carcinoma has resulted in two prospective trials at the Medicine Branch National Cancer Institute. The first trial compared high-dose, split-course intravenous cyclophosphamide with conventional treatment with an oral alkylating agent, melphalan [also called L-phenylalanine mustard (PAM)]. While both regimens were essentially equal in therapeutic efficacy, the former was considerably more toxic and the latter was therefore preferred. The second trial employed a 4-drug combination (5-fluorouracil, methotrexate, cyclophosphamide, and hexamethylmelamine); the results indicated a higher overall response rate (85%) and a higher complete remission rate (31%) with the combination therapy than with the PAM therapy, although the study is short and the observations are preliminary.

Altretamine