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Biomedical subjects

C A Coltman

Publications and source records attributed to C A Coltman.

At least 55 records · Page 3Linked to original sources
PubMed1991

Alternated versus syncopated CHOP-PVB: two studies for the treatment of non-Hodgkin's lymphoma by the Southwest Oncology Group.

Based on a preliminary trial that suggested that CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and PVB (cisplatinum, vinblastine, bleomycin), are at least partially non-cross-resistant, the Southwest Oncology Group treated patients with unfavorable histology, non-Hodgkin's lymphoma with CHOP and PVB. In the first study, 76 eligible patients were given three courses of CHOP, with complete or partial responders receiving three courses of PVB followed by three further courses of CHOP. Nonresponders after the initial three cycles of CHOP, received six courses of PVB. In the second study, 154 eligible patients were treated with alternating cycles of the two drug regimens. The overall objective antitumor response (CR + PR) was 77% for the first study and 58% for the second. The complete remission rates were 48% and 38%, respectively. The overall survival for both studies is similar. These results are interpreted in terms of the Goldie-Coldman hypothesis.

Antineoplastic Agents↗
PubMed1990

Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer. A Southwest Oncology Group Study.

Small cell lung cancer patients who failed primary systemic therapy or who failed after response were randomly assigned to salvage treatment with etoposide (VP-16) and cisplatin (CDDP) or bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC). Good risk patients were those who had tolerated prior chemotherapy well, those who had not had prior radiation therapy, and those who were 65 years of age or younger. Patients with a history of poor tolerance, prior radiation therapy, or those who were older than 65 years of age were classified as poor risk. Forty-five patients were randomized to the BTOC regimen and 58 to the VP-16/CDDP regimen. The overall remission rate was 13% (13 of 103 patients). Good risk patients treated with the BTOC regimen had a remission rate of 27% (three of 11 patients), which was the same rate as patients treated with the VP-16/CDDP regimen (three of 11 patients). Poor risk patients had remission rates of 9% (three of 34 patients) with the BTOC regimen and 9% (four of 47 patients) with the VP-16/CDDP regimen. The median survival time from the start of therapy was 16 weeks for all patients. BTOC good risk patients had a median survival time of 10 weeks, as compared with 14 weeks for poor risk patients. VP-16/CDDP good risk patients had a median survival time of 35 weeks, as compared with 12 weeks for poor risk patients. Although based on small numbers, the advantage in survival time for good risk patients treated with VP-16/CDDP over those treated with BTOC is statistically significant. Prior exposure to VP-16 did not influence the outcome of patients treated with VP-16/CDDP. Both regimens produced moderate toxicity, but were generally well tolerated. It was concluded that VP-16/CDDP may be a useful salvage treatment for good risk patients, despite its limited remission rate. Also, it was found that BTOC has no value for patients in this setting and that neither regimen helps patients who are poor risk.

Adult↗
PubMed1990

Prognostic value of pretreatment serum beta 2 microglobulin in myeloma: a Southwest Oncology Group Study.

Six hundred twelve eligible, previously untreated patients with active multiple myeloma and at least some data available for analysis were entered into a randomized trial (Southwest Oncology Group [SWOG] Phase III myeloma study 8229/30), in which the prognostic significance of pretreatment serum beta 2 microglobulin levels was evaluated. Because there was no statistically significant survival difference between the alternating and syncopating VMCP/VBAP regimens, it was possible to evaluate serum beta 2 microglobulin for the total population all together. The serum beta 2 microglobulin measurements showed the highest significance of any prognostic factor, both in the bivariate and multivariate regression analyses. The median survival was 36 months for the 322 patients with pretreatment serum beta 2 microglobulin values of less than 6 micrograms/mL, as compared with a median survival of 23 months for the 225 patients with a beta 2 level of greater than or equal to 6 mcg/mL (P less than .0001). The stepwise multiple regression model first contained serum beta 2 microglobulin, followed by serum albumin, serum calcium, age, and serum creatinine. Serum beta 2 microglobulin was highly correlated with stage: median values ranged from 3.7 micrograms/mL for stage IA, to 10.1 for stage IIIB. It was possible to stratify myeloma patients based on combinations of serum beta 2 microglobulin with both albumin and age, producing excellent separation of patients into low-, intermediate-, and high-risk categories. It is concluded that serum beta 2 microglobulin is the most powerful prognostic factor currently available for multiple myeloma and that it can be used alone or in combination with other variables for pretreatment stratification.

Age Factors↗
PubMed1990

Phase II trial of intravenous melphalan for metastatic colorectal carcinoma. A Southwest Oncology Group study.

Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity was encountered in the first five patients. Toxicity was primarily myeloid and was moderate to severe in most patients with one treatment related death. There were two complete and one partial response among 43 patients. Melphalan at 30 mg/m2 has little activity among patients with metastatic colorectal carcinoma.

Adult↗
PubMed1990

Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study.

Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty-three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer.

Adult↗
PubMed1990

m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Adolescent↗
PubMed1990

Chemotherapy is superior to sequential hemibody irradiation for remission consolidation in multiple myeloma: a Southwest Oncology Group study.

Six hundred fourteen previously untreated patients with multiple myeloma were evaluated on this phase III Southwest Oncology Group (SWOG) trial. For remission induction, two noncross-resistant drug combinations (vincristine, melphalan, cyclophosphamide, and prednisone [VMCP] and vincristine, carmustine [BCNU], Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and prednisone [VBAP]) were administered with either a direct alternating or a syncopated schedule. Pretreatment serum beta-2 microglobulin (beta 2M) was the single most important prognostic factor for survival (P less than .0001). There was no difference in toxicity, response, or survival by induction chemotherapy schedule (P greater than .7). For consolidation, 180 eligible and responsive patients were randomized to receive either an additional year of VMCP or sequential hemibody radiation (HBI) with vincristine and prednisone (VP) administered between the two HBI courses. Relapse-free survival (26 months) and overall survival (median, 36 months) were better with VMCP than with HBI (median, 20 months and 28 months; P = .04 and .018, respectively). HBI was also evaluated on a nonrandomized basis in 66 patients who achieved either a partial response (PR) or who were nonresponders to induction therapy. While HBI converted 24% of the PR patients to remission status, this effect was only seen in 5% of nonresponding patients. The survival of responsive and nonresponding patients receiving HBI was similar. All HBI groups had an inferior outcome to those receiving VMCP consolidation. Myelosuppression was also significantly worse after HBI. Survival from the time of relapse did not differ between patients randomized to receive VMCP or HBI. Thus HBI induced less durable remissions, but did not render patients less amenable to postrelapse chemotherapy. Our findings do not support the use of HBI in either chemotherapy responsive or nonresponding patients with multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Phase I trial of echinomycin (NSC 526417), a bifunctional intercalating agent, administered by 24-hour continuous infusion.

Echinomycin was administered to 43 patients with advanced cancer in escalating doses ranging from 60 to 2128 mcg/m2. The dose-limiting toxicity of echinomycin administered as a 24-h continuous infusion every 28 days was nausea and vomiting beginning at the end of the 24 h infusion and lasting from 3 to 8 days. Other toxicities included sporadic thrombocytopenia and biochemical evidence of liver dysfunction characterized by elevations in SGOT. Peripheral vein phlebitis was noted in 100% of patients, and watery diarrhea of 24-48-h duration was noted in 7% of patients. The maximally tolerated dose of echinomycin was 2128 mcg/m2. The recommended dose for phase II trials utilizing the 24-h continuous infusion schedule is 1600 mcg/m2 repeated every 28 days with pretreatment antiemetics.

Adult↗
PubMed1989

cis-Diamminedichloroplatinum in the treatment of advanced epidermoid carcinoma of the penis: a Southwest Oncology Group Study.

A total of 26 patients with biopsy proved epidermoid carcinoma of the penis (Jackson stage III or IV) with measurable disease, no prior chemotherapy and adequate renal function received 50 mg. per M.2 cis-diamminedichloroplatinum intravenously on days 1 and 8 of 28-day cycles. There were 4 partial responses (15.4 per cent), with a response duration of 1 to 3 months. The median survival was 4.7 months. This agent cannot be recommended as treatment for advanced epidermoid carcinoma of the penis using this particular dose and schedule.

Carcinoma, Squamous Cell↗
PubMed1989

Phase II evaluation of bisantrene in acute leukemia. A Southwest Oncology Group Study.

Twenty-nine patients with heavily pretreated acute leukemia in relapse were treated with bisantrene (maximum dose 120 mg/m2/day x 5) in a phase II study. Twenty-seven of the 29 patients were evaluable for response, receiving a total of 53 courses of treatment. There were three complete remissions (11%) lasting 27, 107, and 115 days. One brief partial remission of 43 days was also seen for a total response rate of 15%. Toxicity was mainly limited to the expected myelotoxicity with minimal nonhematologic toxicity seen. Although the complete remission rate is low, an antileukemic effect was seen in the majority of the patients treated. Sixty-one percent of the patients had at least a 50% decrease in the circulating blast count and 32% had at least a 50% decrease in the number of bone marrow blasts. We conclude that bisantrene does have an antileukemic effect, but that the optimal starting dose is not yet established.

Acute Disease↗
PubMed1989

Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.

The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain complete remission (CR[u]), be introduced to accommodate the difficulty of persistent radiological abnormalities of uncertain significance.

Hodgkin Disease↗
PubMed1989

Analysis of prognostic factors for the outcome of marrow transplantation or further chemotherapy for patients with acute nonlymphocytic leukemia in first remission.

To test whether variables at diagnosis can identify patients with acute nonlymphoblastic leukemia (ANL) for whom bone marrow transplantation (BMT) is more likely to be of benefit and those for whom continued chemotherapy is a better approach, the association of 15 clinical and laboratory factors with outcome was investigated among 220 patients (ages 1 to 53 years) treated with cyclophosphamide and total body irradiation (TBI) followed by allogeneic BMT, and among 392 patients (ages 13 to 50) administered intensive chemotherapy. In the BMT group, female sex, younger age, the absence of hepatitis during induction, a larger percentage of circulating blasts, and a shorter duration of symptoms were associated with longer survival, whereas only female sex and younger age favorably influenced disease-free survival (DFS). In the chemotherapy group, younger age, lower WBC at diagnosis, a single successful induction course, and the absence of circulating promyelocytes were associated with longer survival, whereas only a lower WBC and a lower percentage of peripheral neutrophils were associated with longer DFS. Estimated regression coefficients for treatment-by-prognostic-factor interactions were used to characterize subgroups of patients in which one treatment or the other produced better outcomes. BMT and chemotherapy produced similar durations of survival in a subset of patients characterized by many or all of the following: older age, male sex, achievement of complete remission (CR) after one induction, and absence of circulating blast cells at presentation. These data suggest that, using pretreatment variables, subgroups of patients can be identified for whom either BMT or continued chemotherapy is most likely to be beneficial.

Adolescent↗
PubMed1988

Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial.

STUDY OBJECTIVE: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. DESIGN: Nonrandomized, phase II clinical trial. SETTING: Tertiary care units in university medical centers. PATIENTS: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. INTERVENTIONS: Patients initially received recombinant interleukin-2, 100,000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100,000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. MEASUREMENTS AND MAIN RESULTS: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 +/- 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 +/- 0.6 X 10(10); and the mean number of interleukin-2 doses administered during the last phase was 10.2 +/- 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. CONCLUSIONS: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.

Adult↗
PubMed1988

Southwest Oncology Group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas.

The Southwest Oncology Group (SWOG) began testing doxorubicin-containing combination chemotherapy in 1972 using the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen. Subsequent studies, including 350 patients followed for up to 13.3 years, demonstrated that CHOP was curative in 32% of advanced stage, diffuse large cell lymphomas. More recently, promising results from several institutions suggest that new combinations including methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone (m-BACOD), prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate (ProMACE-CytaBOM), and methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B) may be superior to CHOP as gauged by complete response (CR) rates. Consequently, the SWOG developed a strategy to compare these regimens directly with CHOP. In 1984 the SWOG began testing these regimens in sequential group-wide phase II trials to confirm therapeutic activity, establish feasibility with regard to toxicity in a cooperative group setting, and gain experience using the complex schedules and dose-modification schemes. Those phase II studies have been completed, and preliminary results indicate that these regimens are active (CR rates, 53% to 65%) and feasible to administer in a cooperative group setting (fatal toxicity, 2% to 6%). We conclude that these three drug regimens can be administered safely in a cooperative group setting, and the CR rates support the current SWOG comparative trial using CHOP as the standard treatment arm.

Antineoplastic Combined Chemotherapy Protocols↗