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Cancer is primarily a disease of the elderly and the palliation of both disease- and treatment-related symptoms is of importance in the practice of cancer medicine in all patients. Many older patients are treated within community hospitals, in which anticancer therapies are less likely to be given and in which the palliation of symptoms should be of primary importance. Many oncologists struggle with the palliation of symptoms in patients who are near the end of life. This is despite the considerable energies that are spent in palliating symptoms in patients who are receiving anticancer therapies at all disease stages. The management of pain has advanced considerably recently with improvements in pain assessment and pharmacologic interventions. However, elderly patients are less likely than younger patients to receive proper pain management. Elderly patients also are less likely to take opioids for pain because of their attitudes and beliefs. Fatigue, dyspnea, and psychologic issues also are of importance in the management of elderly cancer patients both during anticancer therapy and near the time of death. Some elderly cancer patients die in the care of a hospice, although many are not referred to this service. There are many barriers to the provision of palliative medicine and these may be related to health practitioners, to the patients themselves, or to the health care system of which they are part. The increased educational efforts of health professionals are needed to ensure that all patients, including the elderly, have adequate palliation of their cancer-related symptoms.

Background: Over the past 20 years, considerable progress has been made in the early detection and treatment of cancer. Despite these advances, cancer incidence and mortality rates among Native Americans have not kept pace. Cancer centers are in a unique position to offer technical assistance, resources, and a long term commitment that can help address these concerns within tribal communities., Methods: The University of Wisconsin Comprehensive Cancer Center developed a proactive plan to build collaborative partnerships with Wisconsin Native Americans. This began with an outreach plan that prioritized intervention strategies. A Native American health professional was hired to serve as liaison and advocate. Resources were committed, and staff was assigned to work with the community to develop intervention strategies that would be culturally competent and able to address the concerns of community members., Results: Various collaborative activities resulted from these efforts. These included participation in Native American cancer work groups, conferences, and seminars. Most importantly, these efforts resulted in a partnership with the Native American community that is based on honor and mutual respect., Conclusions: Careful planning, prioritization, allocation of resources, and a commitment to Native Americans can result in partnerships with the community and interventions that address their cancer control needs. Building and sustaining these partnerships takes time and thoughtful exploration of issues and concerns to develop mutual trust and respect. Both cancer centers and tribal communities can benefit by recognizing that shared power, as a reciprocal value, can benefit the whole.

The Committee on Treatment acknowledged the paucity of information related to the management of cancer in older patients and identified short-term and long-term efforts to study these issues. Short-term efforts should focus on effects of cancer and cancer treatment on survival and quality of life, efficacy and toxicity of antineoplastic therapy, barriers to adequate treatment, alternative settings of cancer care, and special supportive care needs. Long-term efforts should focus on unique features of cancer in older patients, long-term effects of cancer and cancer treatment, and prevention and detection of new primary malignancies. The Committee recognized that our recent advances in cancer treatment including palliative surgery, limited surgery, radiosurgery, and antidotes to drug toxicity may improve the tolerance of antineoplastic therapy by older patients and be beneficial in terms of survival and quality of life.

Combined modality trials in early breast cancer have been underway since the 1960s and results are available to indicate varying degrees of success in Stage I and II. The trials have involved more than 29,000 women in 61 randomized trials. The recommendations can be summarized by stage, estrogen receptor (ER) status, and menopausal status. In Stage II patients, chemotherapy has an impact on disease mortality for ER-positive and ER-negative premenopausal women and possibly ER-negative postmenopausal patients. In postmenopausal Stage II ER-positive patients, tamoxifen given for more than 2 years has a beneficial effect on survival. In node-negative patients, the major effects have been on improving disease-free survival (DFS) rather than overall survival. Tamoxifen has a positive effect in ER-positive patients while chemotherapy benefits ER-negative patients. In at least one trial chemotherapy benefitted women with ER-positive tumors, both premenopausal and postmenopausal, with lesions larger than 3.0 cm. Ongoing trials are designed to answer questions regarding optimal therapy for varying subsets including those tumors in which ER cannot be measured. New prognostic features used to determine therapy include flow cytometry studies of DNA synthesis and oncogene expression.

Breast cancer is being diagnosed earlier with about 94% of patients presenting with disease limited to the breast or axilla. Despite this trend, more and more patients are receiving adjunctive therapy. In Stage II disease the results of clinical trials suggest that single agent chemotherapy has little if any role in adjuvant therapy. Polychemotherapy can improve survival in premenopausal women with a gain in outcome of about 26%. The duration of therapy appears optimal when given for 6 months. In postmenopausal estrogen receptor-negative women, chemotherapy also has a major role. Tamoxifen appears to offer approximately a 22% improvement in mortality for postmenopausal women. The longer duration of tamoxifen as adjuvant therapy appears to enhance the effect. Premenopausal women may also benefit using tamoxifen but the gain is less clear. Adding tamoxifen to chemotherapy does not enhance the effect. Patients with more than four positive lymph nodes may require more intensive therapy to show a major benefit. Radiotherapy can be integrated along with chemotherapy as adjunctive therapy.

The effective treatment of systemic cancer began in the 1950s on two fronts, i.e., childhood leukemia and choriocarcinoma. These two diseases were successfully treated as a direct result of the use of antifolate methotrexate. The demonstration of complete durable remissions in these diseases quickly led to development of other anticancer drugs, tested using the prospective clinical trials. In the 1960s as the number of active drugs increased, combination chemotherapy was introduced. Other systemic cancers, such as Hodgkin's, large cell lymphoma, and testicular cancer, became curable in the 1970s. For the common low-growth fraction solid tumors, the curability of systemic disease remained elusive until the introduction of adjuvant therapy to treat micrometastases. The past decade of the 1980s has seen improvement in the outcomes for breast cancer, osteosarcoma, and possible colon cancer utilizing adjunctive chemotherapy. The 1980s also saw the introduction of biologic therapies that have further improved the outcomes of several leukemias and produced consistent responses in patients with renal cell and melanoma. The 1990s will undoubtedly see more improvements as the effects of current drugs will be enhanced not only by improved integration of systemic and local therapies but also by utilizing cytokines and biologic response modifiers in concert with cytotoxics. Moreover, as we understand more about the process of cancer induction, promotion, and progression, more specific anti-cancer approaches will be developed to control cancer even before clinical cancer is diagnosed. Underlying and facilitating the improvement in cancer therapy have been not only the experimental results of many laboratory scientists but also the outcomes from many controlled clinical trials, the laboratory of clinical scientists.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.

Of 86 patients entered in an Eastern Cooperative Oncology Group (ECOG) random Phase II study of mitoxantrone (DHAD) and cisplatin (DDP) in primary liver cancer, 69 were eligible. Nine of the 13 ineligible patients were excluded after a pathology review. Sixty-one percent of the patients were North American, and 39% were South African. The most common severe or the worst toxicity on DHAD was hematologic; and to DDP, hematologic and vomiting. Of the 69 eligible patients, 21 experienced severe, life-threatening or fatal toxic reactions. Two patients treated with DDP had partial responses. With a 95% confidence interval, the true response rate to DHAD was less than 8%, and to DDP, less than 17%. The median survival time was 14 weeks on both drugs. Assuming a proportional hazards model, factors that are significantly associated with survival are patient performance status, the presence of the symptoms, raised bilirubin and hepatomegaly, and clinical evidence of cirrhosis. Any differences between survival rates for South African and North American patients were largely explainable by these factors.

Nineteen studies of advanced cancer in 8 disease sites have been examined using data from the Eastern Cooperative Oncology Group. The purpose of the investigation was to determine susceptibility of elderly patients (greater than or equal to 70 years of age) to cancer chemotherapy and to compare the results with corresponding figures in control patients (less than 70 years of age). The results indicate that in general, the elderly patients have identical rates of severe toxicity as their younger counterparts. The only exception is for hematologic reactions in a few of the sites studied. On closer examination, the agents that appear to be responsible for these especially adverse effects are methotrexate and methyl-CCNU. It is demonstrated that the elderly patients have similar response rates and survival expectancy to the nonelderly patients. Consequently, it is concluded that the apparent discrimination in not treating elderly patients as aggressively as younger patients, and in excluding elderly patients from protocols, does not appear to be justified. Exclusions should be based on physiologic functional parameters, such as measures of renal, liver and marrow function, or performance status, rather than on an arbitrary age limit. Exceptions should only be made for agents which have a clearly demonstrated adverse effect on the elderly.

Chemotherapy once relegated to end stage patients has markedly improved with the use of combinations. Response rates with single agents have improved from 15 to 35%, to 50 to 70%, using combinations with an increase in complete response rates to about 25%. A series of four studies completed by the Eastern Cooperative Oncology Group over the past eight years typifies the improvement in response rates achieved by combinations as compared to single agents. Survival gain can be demonstrated for responders vs non-responders; however with current combinations, there is an apparent plateau in response rates (55 to 60%), durations of response (eight months) and survival for responders (18-22 months) as compared to survival of non-responders (six to eight months). Further improvement in response rates may occur by searching for new agents, combining hormonal and immunostimulation with chemotherapy or by sequencing non-crossresistant combinations. However, since most patients with breast cancer present with local or regional disease but go on to die of disseminated cancer, major improvements in survival are most likely to occur by treating this neoplasm as a systemic disease through cobmining effective local therapy with systemic treatments.

The Eastern Cooperative Oncology Group has studied 113 patients with generalized progressive malignant lymphomas in a randomized clinical trial. Pathologic diagnosis was subclassified by cell type and nodal pattern by The Pathology Panel for Lymphome Clinical Trials. Patients were randomly assigned treatment with either cyclophosphamide (C), vincristine (O), and prednisone (P) (COP) or CO without prednisone. Initial treatment was given for 8 weeks and further randomization of responders to observation or additional chemotherapy was carried out. A significant difference in complete remission rate between treatments was shown: with COP, 43%, and with CO, 17%, indicating an important role for prednisone in inducing CR. COP was also associated with longer remission durations and improved survival. Complete remission following initial chemotherapy is also associated with longer duration of disease-free time and survival. The initial pathologic cell types and nodal pattern also strongly influence survival. Extended "maintainence" CO treatment improved disease-free remission duration, but not survival.

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.

34 patients with the diagnosis of diffuse well-differentiated lymphocytic lymphoma (DLWD), confirmed by a Pathology Panel, who were entered on a previously reported Eastern Cooperative Oncology Group study (EST 1472), were analyzed for response and survival. The response rates were as follows: CR 32%, PR 39%, NC or PD 29%. Survival analysis according to chemotherapy response revealed an estimated two-year survivorship of CR 89%, PR 65%, NC 69%, and PD 44%. Comparison with NLPD entered on the same study showed a two-year survival of 83% for NLPD and 67% for DLWD, indicating significantly poorer survival for DLWD as compared to NLPD (p less than .05). Median survival for DLWD from diagnosis was 39.0 + months. The presence of lymphocytosis over 4000/mm3 had little effect on response rates or survival. We conclude that DLWD is a less favorable lymphoma type than NLPD and should be treated with aggressive chemotherapy since achievement of CR seems to effect survival favorably.

This is a comparative study to evaluate response rate to mitoguazone (MGBG) and vinblastine (VLB) in 52 evaluable patients with advanced transitional cell carcinoma of the urinary tract. Of 38 patients with measurable disease, two of 18 (11%) on MGBG had partial remission (95% confidence interval: 0.01, 0.35), whereas four of 20 (20%) responded on the VLB arm (95% confidence level: 0.06-0.44). Both responses on the MGBG arm were seen in patients given prior chemotherapy. Side effects of both drugs were significant, with 46% of patients given VLB developing severe or life-threatening hematologic toxicity. Data indicate that both drugs, as single agents, are probably inferior to cisplatin for control of advanced transitional cell carcinoma of the urinary tract.

One hundred and sixteen patients with advanced and metastatic adenocarcinoma of the pancreas were randomized to treatment with combined Streptozotocin and 5-fluorouracil or combined Streptozotocin and cyclophosphamide. Toxic reactions to each regimen were qualitatively similar and consisted of nausea and vomiting during the time of treatment and subsequent leukopenia and thrombocytopenia. Renal toxicity was less frequent and only rarely severe. Among 51 eligible and evaluable patients treated with the Streptozotocin-cyclophosphamide combination, 12% showed objective response and among 42 patients treated with Streptozotocin + 5-fluorouracil, 12% showed objective response. The Streptozotocin + 5-fluorouracil-treated patients showed a slight advantage in survival. Neither regimen can be considered of substantive value to the patient with advanced pancreatic carcinoma.

Eighty patients with nodular mixed lymphocytic-histiocytic lymphoma (NM) entered on four different Eastern Cooperative Oncology Group chemotherapy studies were analyzed for response and survival. They were compared with 249 patients with nodular lymphocytic poorly differentiated lymphoma (NLPD), who were treated similarly. The response rates in NM were: CR 45%, PR 30%, NC-PD 25%. In NLPD the quality of response had little effect on survival (CR 91%, PR 90%, NC-PD 76%), whereas in NM the two year survivorship of 85% for CR dropped drastically to 33% for the partial responders (P less than 0.01). Ninety percent of the previously untreated NLPD, but only 59% of the comparable group of NM, survived 2 years. In 23 patients with NM in which the pattern was reported as both nodular and diffuse (ND-M), the 2-year survival of 35% was markedly inferior to a 66% 2-year survivorship observed in 57 patients with the pure nodular pattern (P less than 0.05). It appears that NM is a less favorable lymphoma type than NLPD. In NM achievement of a CR affects survival favorably; consequently, the use of aggressive chemotherapy regimens in an attempt to achieve high rates of CR are recommended. In NLPD, on the other hand, since survival curves of partial and complete responders are almost identical, suboptimal treatments may be justified.

Response and survival were analyzed in 97 patients with NLPD (Nodular Lymphocytic Poorly Differentiated Lymphoma) and 77 with DLPD (Diffuse Lymphocytic Poorly Differentiated) treated by intensive versus moderate chemotherapy regimens. The complete and overall response rate in NLPD of 47% and 81% was significantly superior to 25% and 59% obtained in DLPD. The estimated two year survival of 83% in NLPD was also significantly superior to 47% two year survivorship of DLPD (p less than .001). The chemotherapy responsiveness had a significantly favorable effect on DLPD survivorship with two year survivals of 84% for CR, 58% for PR and 17% for PD. In NLPD the effect of chemotherapy responsiveness on survival was less striking (CR 91%, PR 85%, and PD 72% surviving two years). The data, in our opinion, confirm the rationale for the use of aggressive multiple agent chemotherapy regimens in DLPD where achievement of compelte response appears to be the single most important factor in improving survivorship. On the other hand NLPD, with excellent survival rates which appear to be only partially dependent on chemotherapy responsiveness might serve as an ideal model for moderate intensity or single agent chemotherapy trials.

Eastern Cooperative Oncology Group experience in the clinical application of the Rappaport Classification on Non-Hodgkin's lymphomas (NHL) is reviewed in 670 cases studied since 1972. The diagnoses of institutional pathologists were reviewed by the Pathology Panel and Repository Center for Lymphoma Clinical Studies. Diagnostic agreement in regard to histologic pattern (nodular versus diffuse) was excellent (90%) but was less favorable when concurrence as to both pattern and cell type was assessed (82% in NLDP and 60% or less in other subtypes). Disagreement in regard to NHL diagnosis is related to the complexity of present nomenclature and to the lack of support of pathology activities within cooperative groups. It is suggested that patients entered into group NHL studies be randomized into favorable and unfavorable groups, primarily on the basis of histological pattern.

Twenty Malaysian patients with unresectable primary liver cell cancer were prospectively studied at the General Hospital, Kuala Lampur, and were compared for clinical features with an equal number each of African and American patients being studied by the Eastern Cooperative Oncology Group. The patients received intravenous 5-FU and oral MeCCNU which was used for the first time in an Asian country. Most of the Malaysian patients were Chinese, belonged to younger age groups, and presented with massive hepatomegaly, jaundice, and fever. Toxicity to MeCCNU invariably occurred in the form of leukopenia or thrombocytopenia, but none life threatening. Partial response was seen in 20% of Malaysians as compared to 16% in Americans and none in Africans. Malaysians achieved a median survival of 16 weeks compared to 28 weeks in Americans and only eight weeks in Africans. Malaysian Chinese patients were all HBc Ab + ve. Other factors which may have played an etiologic role in the induction of primary liver cancer included alcohol, Chinese herbal medicines, aflatoxin and habitual use of medicated rubbing oils.

The Eastern Cooperative Oncology Group, composed of major cancer treatment centers, has an outreach program which involves community hospitals in ongoing cancer clinical trials. A prevalence survey was carried out in February 1981 among 104 community hospitals and 21 member institutions to determine the characteristics of patients being treated, their staffing, and reasons why patients were not on protocol studies. The survey sampled 25 (50) consecutive patients from community hospitals (member institutions). The purpose of the study was to assess the impact of a community cancer control program. The results of the study demonstrated that 16% of patients surveyed in the affiliated community hospitals were being treated on a research protocol. In addition, a further 35% had their treatment plan influenced by a protocol. Consequently protocols have impacted directly or indirectly on 51% of the patients. The corresponding figures in member institutions were 23% and 38% for a total of 61%. In studying protocol availability, it was found that 66% of all patients were ineligible for any protocol. Of patients eligible for a protocol but not registered on one, 52% were not registered because of physician preference for a specific treatment. The affiliates surveyed were shown to be on average half as large as member institutions in terms of number of beds and staff size. Also, staff/patient ratios are generally smaller in the community hospitals. The median age of patients was considerably lower than SEER incidence data. Also, elderly patients were slightly more prevalent in community hospitals than in member institutions. A clear relationship between disease stage and age in breast cancer patients was noted with the representation of early-stage disease much higher in young women.

Data on 162 women (90 premenopausal and 72 postmenopausal) with metastatic breast cancer randomized to receive cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF) on two Eastern Cooperative Oncology Group (ECOG) protocols were analyzed. Twenty-three percent had complete remission; 39% had partial remission; 28% had no change; and 3% had disease progression. Of those patients in whom receptors were known, response rates were 65% for estrogen (ER)-receptor positive and 70% for ER-negative patients. The median duration of response was 11.4 months. The median survival time from the start of CAF was 20.2 months. The response rate, time to treatment failure (TTF), and median survival time were superior in the premenopausal women. These differences ceased, however, to be statistically significant in logistic models. Factors significantly associated with longer TTF and longer survival were as follows: one or two organs with metastases (TTF, P less than 0.0001; survival, P less than 0.0001); dominant site other than soft tissue (TTF, P less than 0.0001; survival, P = 0.05); and an initial good performance status (TTF, P = 0.007; survival, P = 0.02). Patients with ER-positive disease had a significantly longer median survival time (P = 0.003).

Although breast cancer presents as localized disease and is treated with local modalities, i.e. surgery and radiotherapy, patients die with metastatic disease. For patients with positive nodes, the recurrence rates are well known. It is this group of patients who should receive more aggressive treatment. Chemotherapeutic regimens are available that cause responses in patients with advanced disease in the range of 20% to 65%, with about 15% complete responses The current paper deals with the application of several chemotherapeutic regimens at the time of surgery in those patients at high risk. The preliminary results indicate a significant decrease in the recurrence rates. Additional studies combining chemotherapy and hormonal procedures are mentioned.

One-hundred and fifty-one adults with acute non-lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST-1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases, Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigator's diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of less than 3 weeks. Age less than 60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparble. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.

A case of spontaneous remission in a Stage IIA diffuse large cell lymphoma is presented. Review of the literature suggests that whereas spontaneous regressions are a well-recognized phenomenon in indolent lymphomas, it is extremely rare in lymphomas of aggressive histologic subtype.

A case report of a patient who developed acute myelogenous leukemia 15 years after injection of Thorotrast and who has been in a sustained long term remission for 14 years is presented with a review of the problems associated with Thorotrast, subsequently shown to be radioactive with long term sequelae.

Tamoxifen and trioxifene are antiestrogens that appear to have different endocrine effects when tested in rats. Whereas tamoxifen has considerable clinical activity, trioxifene is a new antiestrogen with undefined clinical activity. Thirty-six patients were treated with graded doses of trioxifene. The low-dose group (0.5 to 12 mg/m2 twice daily) had a 21% response rate in 24 subjects, and the high-dose group (40 to 100 mg/m2 twice daily) had a 33% response rate in 12 patients (P = 0.13). The time to treatment failure was 67 days and 178 days for the low- and high-dose groups, respectively. Toxicities were non-dose dependent; those of moderate frequency included leukopenia (41%) and nausea (31%). Tamoxifen reduced both prolactin and inducible growth hormone (GH). Trioxifene, although reducing prolactin, differed from tamoxifen in that an increase in inducible GH occurred. Furthermore, a striking dose-dependent decrease in luteinizing hormone and lesser decrease in follicle-stimulating hormone occurred only in the trioxifene-treated patients. This implies an intrinsic estrogenic action of trioxifene in man. Trioxifene is no more efficacious than tamoxifen and has more toxicity.

One hundred and sixty-eight patients with unresectable primary liver cancer were prospectively studied by members of the Eastern Cooperative Oncology Group. These patients were randomized to receive treatment with oral 5-Fluorouracil (5FU), oral 5-Fu plus Streptozotocin, oral 5-Fu plus Methyl-CCNU or Adriamycin. The single agent treatments (oral 5-Fu and Adriamycin) were associated with less gastrointestinal toxicity than were the oral 5-Fu treatment combinations. A total of 15 partial responses were reported. Adriamycin appears to be the most active agent and responsible for 9 of the 15 responses. No response was seen in any of the 48 patients randomized to oral 5-Fu alone. The survival associated with oral 5-Fu alone was significantly shorter than the survival time associated with the remaining 3 treatment programs among both North American and South African patients. A multivariate model of survival was formulated. Covariates of prognostic significance were treatment, initial performance status and sex. South African black patients had a shorter survival time than North American black patients. Excluding oral 5-Fu from consideration, prognostic variables appeared to dominate any differences between the remaining treatments under study.