Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.

Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity.

Activity of mitoxantrone in a human tumor cloning system.

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracenedione derivative, Mitoxantrone. The object was to determine if the system is useful for pinpointing the types of tumors in patients which should be studied in early Phase II clinical trials. Tumors from 267 patients were placed in culture (20 different histological tumor types). One hundred seventy tumors both grew and formed enough colonies for drug sensitivity assays. Excellent in vitro antitumor activity was noted for Mitoxantrone against human adenocarcinoma of the lung, small cell lung cancer, melanoma, and biliary tree cancer. Good antitumor activity was noted against breast cancer, ovarian cancer, non-Hodgkin's lymphoma, head and neck cancer, squamous cell lung cancer, soft tissue sarcoma, gastric cancer, and hepatomas. The drug showed no in vitro activity against colon cancer. These data indicate that Mitoxantrone has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of Phase II clinical trials with the drug should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of a new compound.

Utilization of a human tumor cloning system to monitor for marrow involvement with small cell carcinoma of the lung.

We have compared the sensitivities of two methodologies for determining bone marrow involvement by small cell lung cancer. These methodologies included histological examination of marrow aspirations and biopsies versus growth of tumor colonies in soft agar. There were four instances in which histological study of the marrow aspirate (and biopsy) revealed metastatic small cell lung cancer. All four of the specimens formed colonies in soft agar. Thirty-four of 37 histologically negative aspirations and biopsies) showed no growth in the soft agar system. However, three histologically negative specimens formed colonies in soft agar. The cells growing in these colonies were documented to be small cell lung cancer by histology and growth in nude mice. We conclude that small cell lung cancer metastatic to bone marrow will form colonies in soft agar. Additional study is needed to determine if the soft agar system is indeed more sensitive than routine histology in detecting small cell lung cancer metastatic to bone marrow.

Phase I clinical investigation of 1,4-dihydroxy-5,8-bis (( (2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride (NSC 301739), a new anthracenedione.

1,4-Dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)-amino))-9,10-anthracenedione dihydrochloride is a new anthracenedione derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection, repeated at 4-week intervals. Twenty-five patients received a total of 41 courses of the drug in a dose range of 1.2 to 14 mg/sq m. Leukopenia and thrombocytopenia were dose limiting but were of short duration and rapidly reversible. Mild degrees of phlebitis were observed in 10% of courses, and a green discoloration of the urine was noted with doses of greater than or equal to 10 mg/sq m. One patient with adenocarcinoma of the lung experienced a partial response of his tumor secondary to the drug. Phase II studies of 1,4-dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)amino))-9,10-anthracenedione dihydrochloride are planned at a starting dose of 12 mg/sq m as a single dose repeated at 21- to 28-day intervals.

Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942).

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.

Effect of initial resection of small-cell carcinoma of the lung: a review of Southwest Oncology Group Study 7628.

The role of surgery in small-cell carcinoma of the lung (SCCL) has been recently re-evaluated. We reviewed the records of 262 patients with limited SCCL on Southwest Oncology Group (SWOG) protocol 7628. Fifteen patients were identified who presented after surgical resection (12 lobectomy, three pneumonectomy). All patients were subsequently treated with chemotherapy, radiotherapy +/- immunotherapy (BCG). Median survival time was 10.5 months. Median survival time of patients with initial surgical resection was 25 months (P = .004). Forty-five percent of the surgical patients were alive at two years v 13.7% of the nonsurgical patients (P less than .05). A second subgroup of 33 patients was identified with small primary tumors who did not undergo surgical resection. Median survival time in this group was ten months (P = .03). Site of initial relapse was clearly documented in 142 patients. Fifty-six percent of patients not receiving surgery had initial relapse within the chest compared to 13% of patients undergoing surgery (P = .002). Whether the survival benefit identified was caused by or was incidental to surgical resection of the primary lesion remains to be determined in randomized prospective trials of operable candidates.

A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study.

Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage.

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.

Comparison of young clinical investigators' accuracy and reproducibility when measuring pulmonary and skin surface nodules using a circumferential measurement versus a standard caliper measurement: American Association for Cancer Research/American Society of Clinical Oncology Clinical Trials Workshop.

PURPOSE: The clinical investigator must understand that errors in measuring tumors can greatly affect such clinical-trial end points as tumor response. We performed a prospective, controlled study of tumor measurements that compared circumferential measurements made with a loop planimeter with linear measurements made with a standard caliper. METHODS: Using a cross-over design, 76 clinical oncology fellows/junior oncology faculty members attending a Methods in Clinical Cancer Research Workshop sponsored by the American Association for Cancer Research and the American Society of Clinical Oncology measured five pulmonary nodule phantoms that ranged in size from 1.76 to 13.21 cm(2) and five surface nodule phantoms with sizes ranging from 2.3 to 12.9 cm(2). To perform these measurements, they used both a loop planimeter and a caliper. Forty-two and 40 participants repeated measurements 3 days later on pulmonary and surface nodules. Accuracy, reproducibility, and time efficiency were evaluated. RESULTS: The linear caliper measurements overestimated pulmonary nodule and surface nodule size by a median of 37% and 23%, respectively. Circumferential loop planimeter measurements overestimated pulmonary nodule size and surface nodule size by a median of 8% and 17%, respectively. Interobserver reproducibility for the planimeter was greater than that for the caliper, as evidenced by thinner measurement interquartile ranges. Furthermore, intraobserver reproducibility was higher for the planimeter, with its variability being only 31.4% and 25.5% as large as that of the caliper when measuring the pulmonary and surface nodules, respectively. CONCLUSION: Circumferential measurements provide better accuracy, reproducibility, and speed in measuring both pulmonary and surface nodules than do perpendicular diameters.

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.

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.

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.

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.

Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung. A Southwest Oncology Group Study.

Using a randomized prospective trial design, chemotherapy with 5-fluorouracil, vincristine, and mitomycin C (FOMi) was compared with cyclophosphamide, doxorubicin, and cisplatin (CAP) and with FOMi alternating with CAP (FOMi/CAP) in 452 eligible patients with metastatic large-cell undifferentiated and adenocarcinoma of the lung. Objective responses were obtained in 26%, 17%, and 22% of patients treated with FOMi, CAP, and FOMi/CAP, respectively. The median survival was similar for FOMi, CAP, and FOMi/CAP therapies (20, 24, and 23 weeks, respectively), but the overall survival (log rank test), 1-year survival, and remission duration were longer for FOMi/CAP-treated patients. Survival was significantly longer for fully ambulatory FOMi/CAP-treated patients compared with either FOMi (P = .01) or CAP (P = .04). Younger patients treated with full doses of therapy responded more often than older patients receiving reduced drug doses (26% and 11%, respectively; P = .003). A prognostic factor regression analysis of all eligible patients indicates that sex, performance status, stage, and treatment assigned were important independent variables determining survival (P less than .05). Toxicity was comparable in each treatment group.

Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.

In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Profile of men randomized to the prostate cancer prevention trial: baseline health-related quality of life, urinary and sexual functioning, and health behaviors.

PURPOSE: To describe men who agreed to be randomized to the Prostate Cancer Prevention Trial (PCPT), a 7-year, double-blind placebo-controlled study of the efficacy of finasteride in preventing prostate cancer. METHODS: Comprehensive health-related quality-of-life data are presented for 18,882 randomized PCPT participants. RESULTS: PCPT participants are highly educated, middle to upper income, and primarily white (92%). Participants reported healthy lifestyles. The mean American Urological Association Symptom Index score was well below the maximum entry score of less than 19; existing urinary symptoms were generally not bothersome. The scores for two sexual functioning scales could range from 0 to 100, with higher scores reflecting worse sexual functioning. The mean score for the Sexual Problem Scale was 19.2 out of 100, and the mean Sexual Activities Scale was 44.1 out of 100. Scores for seven of the eight Medical Outcomes Study 36-item Short-Form Health Survey scales (higher scores are better) were 10 to 20 points higher than those reported by a general population sample and differed minimally by race but not by age. Previously reported associations between sexual dysfunction and hypertension, diabetes, and depression were also observed. Men who never smoked reported less sexual dysfunction than did those who either had quit or still smoked. CONCLUSION: Individuals who are likely to enroll in primary prevention trials have a high socioeconomic status, healthy lifestyle behaviors, and better health than the general population. These data help oncologists design chemoprevention trials with respect to the selection of health-related quality-of-life assessments and recruitment strategies.

Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance.

Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic intrathecal therapy in AML? (iii) Does late intensification affect treatment outcome? (iv) Does maintenance with levamisole affect disease-free survival or overall survival? Among 611 evaluable patients, 329 (54%) achieved complete remission. There was no difference in the remission rate between those patients receiving rubidazone (54%) and those receiving adriamycin (54%) as part of the induction regimen. Prophylactic intrathecal therapy with cytosine arabinoside had no effect on the incidence of central nervous system disease or survival. After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone). T patients randomized to late intensification had better survival and disease-free survival, compared to those randomized to receive no late intensification (p = 0.027 and 0.030, respectively). At twelve months of remission, surviving patients were randomized to receive levamisole or no further treatment. There was no evidence that levamisole affected survival or disease-free survival.

Splenectomy, chemotherapy, and survival in Hodgkin disease.

The question was raised whether routine splenectomy might, by virtue of its effects on the receipt of subsequent chemotherapy, offer long-term benefits to patients with advanced Hodgkin disease. Therefore, we compared followup data from a group of patients who were receiving mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone (MOPP regimen) and who had had splenectomies to a group of similarly treated, carefully matched control patients on the MOPP regimen who had not had splenectomies. Our results indicate no important difference in duration of survival or long-term remission status. There was only a suggestion that splenectomy in such patients may be followed by impaired resistance to subsequent infections. Therefore, although early splenectomy can be important in the assessment of splenic disease, it must not be considered to be a therapeutic procedure per se.

Chemotherapy of acute leukemia: a comparison of vincristine, cytarabine, and prednisone alone and in combination with cyclophosphamide or daunorubicin.

Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP). Cytarabine was infused continuously for five days. Patients entering complete remission randomly received maintenance treatment with COAP or OAP. For 197 previously untreated AML patients given COAP, DOAP, or OAP, remission rates were 37%, 35%, and 43%, respectively; median lengths, 40, 45, and 90 weeks; median survival, 7, 11, and 8 weeks. No statistically significant difference was found among treatments. Therefore, adding cyclophosphamide or daunorubicin, or using the COAP regimen with continuously infused cytarabine, produced no significant improvement over previously reported regimens. There was no significant difference in remission lengths in previously untreated AML patients maintained on OAP (median 81 weeks) or COAP (median 65 weeks).

Southwest oncology group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas.

Previous studies have established CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as the standard of comparison for treatment programs for patients with advanced stages of aggressive non-Hodgkin's lymphomas. Three sequential CHOP studies conducted by the Southwest Oncology Group (SWOG) showed a complete remission (CR) rate of 53% for 418 patients. This rate did not vary among the three studies. Median age was over 55 years. Relapse-free survival of CRs plateaued at 4 to 5 years. Approximately 21% of all patients in the first study and 33% of all patients in the following two studies are long-term survivors and presumed cured. Survival was clearly a function of patient age. Approximately 45% of all patients under age 55 at the time of treatment are cured by CHOP chemotherapy. To determine the toxicity, CR rate, and patient survival of m-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone), ProMACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin), SWOG initiated a series of phase II studies. Of 118 eligible patients in the m-BACOD study, the median age of 85 patients treated with the full-dose regimen was 54 years, while the median age of 33 patients who started therapy at reduced doses was 67 years. Fatal toxicity was observed in 6% of patients receiving full doses and 13% of those receiving reduced doses. Life-threatening toxicity occurred in 31% of patients on the full-dose regimen and 34% on the reduced-dose regimen. CR was 65% for full-dose treatment, but 27% for reduced doses.(ABSTRACT TRUNCATED AT 250 WORDS)