Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer.

PURPOSE: This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response. MATERIALS AND METHODS: One thousand three hundred fifty four women with measurable disease, previously untreated by hormonal or chemotherapy for advanced or recurrent breast cancer, were enrolled by 179 institutions in 35 countries. Patients were stratified at baseline for menopausal status. Patients receiving adjuvant hormonal therapy within I year were excluded. All patients gave written informed consent, were randomized to 40mg droloxifene or 20 mg tamoxifen daily as single-agent therapy and underwent tumor assessment every 3 months. A central committee reviewed digitized images for all cases of tumor progression or objective response. RESULTS: The hazard ratio (droloxifene/tamoxifen) for the primary endpoint, time to disease progression, was 1.287 favoring tamoxifen (95% C.I.: 1.114-1.487; p <.001). The objective response rate (CR+PR) was 22.4% for droloxifene and 28.6% for tamoxifen (p = .02). Tamoxifen was superior to droloxifene overall, among both pre- and postmenopausal patients and among patients < or =65 years; there was no difference among women >65 years. The hazard ratio for all-cause mortality was 0.871 (95% C.I.: 0.672-1.129; p = .29), favoring droloxifene but not statistically significant. CONCLUSIONS: Droloxifene was significantly less effective than tamoxifen overall and particularly among women under 65 years. Tamoxifen and droloxifene were both less effective in pre-menopausal women with receptor-positive disease compared to post-menopausal women. Further clinical development of droloxifene was stopped.

Development of three African language translations of the FACT-G.

This pilot study investigated the feasibility of translating a quality of life instrument, the Functional Assessment of Cancer Therapy--General version (FACT-G) and the breast cancer version (FACT-B), which consists of the FACT-G plus 10 additional items, into three South African languages (Pedi, Tswana, and Zulu). The international, interdisciplinary research team hypothesized that we could develop reliable and valid translations, and that valuable information could be gleaned from the responses of the three groups of traditional African people, which could inform the Western-trained medical profession. Understanding of cross-cultural views of cancer including its diagnosis and treatment could lead to better communication between the two cultures (Western and Traditional) resulting in increased utilization of Western medical treatment and increased treatment compliance by three of the underserved black populations. A total of 167 respondents completed one of three translated questionnaires, which assessed the patients' quality of life in 5 domains: Physical Well-Being, Social and Family Well-Being, Relationship with Doctor, Emotional Well-Being, and Functional Well-Being, plus for breast cancer patients the additional items on the FACT-B. However, only the items from the FACT-G (the 'core' of the FACT-B) were statistically analyzed for this pilot project. Results showed that it was possible to develop a reliable instrument in the three languages by modifying the standard translation methodology. Translation of physical and functional concepts was most straightforward. Translation of emotional items posed some difficulty. As expected, based upon observations about cultural differences in social values and functioning, the Social/Family Well-Being subscale was problematic. Analysis of this subscale provides information on cultural differences which may be important to physicians desiring to effectively treat this population with sensitivity and dignity. Methodology may be generalizable to other third world patient populations in translation of existing health status questionnaires.

Dose-dependent hormonal effects of toremifene in postmenopausal breast cancer patients.

PURPOSE: The purpose of the study was to compare hormonal effects of three toremifene doses, 20 mg (TOR20), 40 mg (TOR40) and 60 mg (TOR60) administered daily, in postmenopausal women with advanced breast cancer. METHODS: The study was randomized and open label in three parallel groups. Biochemical variables were identified as the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone binding globulin (SHBG). The changes were compared with objective clinical responses and to progression-free time. Adverse reactions and liver function test (aspartate aminotransferase, ASAT) were assessed for safety. RESULTS: A total of 260 patients were randomly grouped (90 to TOR20, 81 to TOR40 and 89 to TOR60). Of these patients 29, 29 and 22 completed at least 3 months of treatment and the results were analyzed for biochemical variables. All treatments had intrinsic estrogen agonist activity by decreasing of serum FSH and LH and by increasing of SHBG during the first 3 months (P < 0.01). Dose TOR20 showed slightly longer times to exert maximum estrogenic effects than did the two higher doses. No increases in liver function tests were seen in any of the groups. Objective response rates were 24.4, 39.5 and 32.6% (P = 0.01) and median times-to-progression were 206, 189 and 196 days in TOR20, TOR40 and TOR60, respectively (P = 0.913). Fewer responses were observed in the TOR20 group than in TOR40 (P = 0.05). Adverse events were reported in 19, 23 and 30 patients in the treatment groups (P = 0.20). The most frequently reported events were hot flushes and nausea. These were mostly mild or moderate, and only 1.5% of treatments was discontinued due to toxicity. CONCLUSIONS: Toremifene doses of 40 and 60 mg daily were effective and safe treatments of breast cancer in postmenopausal women, and no differences in their biochemical or clinical effects were seen. Toremifene at 20 mg/day had similar but slightly less potent antiestrogenic and estrogenic effects than the two higher doses.

Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study.

PURPOSE: Although hormonal therapy represents standard therapy for metastatic hormone-sensitive disease, many patients receive initial chemotherapy because of the location, bulk, or aggressiveness of their disease. It is uncertain whether simultaneous hormonal therapy provides additional benefit compared with chemotherapy alone. Eastern Cooperative Oncology Group trial E3186 was initiated to explore this question. PATIENTS AND METHODS: Between January 1988 and December 1992, 231 patients with estrogen receptor (ER)-positive or ER-unknown metastatic breast cancer were randomized to receive either chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil ¿CAF) or chemohormonal therapy (CAF plus tamoxifen and Halotestin ¿fluoxymesterone; Pharmacia-Upjohn, Kalamazoo, MI ¿CAFTH) as front-line therapy for metastatic breast cancer. Patients who experienced a complete response to induction therapy either received or did not receive maintenance cyclophosphamide, methotrexate, fluorouracil, prednisone, and TH as a secondary randomization. RESULTS: The response rates (complete response and partial response) of patients who received CAF and CAFTH were similar (69.2% v 68.9%, respectively; P =.99). Time to treatment failure (TTF) was slightly longer for patients who received chemohormonal therapy compared with chemotherapy alone patients (13.4 months v 10.3 months, respectively; P =.087), and TTF was significantly longer in ER-positive compared with ER-negative patients (17.4 months v 10.3 months, respectively; P =.048). However, ER status had no effect on overall survival (30.0 months for CAF v 29.3 months for CAFTH). CONCLUSION: In patients with potentially hormone-sensitive metastatic breast cancer, chemohormonal therapy prolongs TTF for ER-positive patients without improving overall survival.

A phase II evaluation of clofazimine plus doxorubicin in advanced, unresectable primary hepatocellular carcinoma.

The riminophenazine compound clofazimine has been shown to be a potent inhibitor of hepatocellular carcinoma (HCC) in vitro. Therapeutic benefit was claimed for patients with HCC treated with clofazimine in a recent clinical trial. The current trial was initiated to evaluate response and survival of patients with HCC receiving clofazimine plus doxorubicin. Twenty-eight patients were entered into the study, of whom 27 were evaluable for response and survival. No patients had a complete or partial response, and 9 had stable disease. The median survival time was 7 weeks. Toxicity was mild with yellow pigmentation of the skin resulting from the clofazimine, and leukopenia, nausea, vomiting and mucositis as expected from doxorubicin. Further studies using other riminophenazine compounds are warranted.

Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group.

PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

Morphology and other prognostic factors of hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma is a malignancy found worldwide that has typically poor prognosis despite treatment. Although several studies have dealt with prognostic factors, just a few detailed analyses of large series correlating the pathology of hepatocellular carcinoma with prognosis are available. The present study was undertaken to address this limitation. PATIENTS AND METHODS: Our prior clinical study described 432 patients, but sufficient tissue was available for evaluation in only 299 patients. Of these, 224 samples contained primary hepatocellular carcinoma, while the remainder contained only metastatic tumor. Characteristics evaluated included degree of tumor differentiation, associated cirrhosis or hepatitis, presence of cytoplasmic inclusion bodies, and blood vessel invasion by the neoplasm. RESULTS: Of the 224 patients, 71% were male, 65% white, and 73% over the age of 45 years. Ninety-one percent were from North America. A total of 42 patients were found to have cirrhosis. Thirty-five percent had cytoplasmic inclusion bodies, and 25% showed evidence of blood vessel invasion. Tumor response rates (tumor shrinkage) were low (8%) regardless of treatment. Presence of cytoplasmic eosinophilic inclusion bodies and blood vessel invasion were not associated with increased survival. Some histopathologies (pelioid, spindle cell, fibrolamellar) were associated with a better prognosis. Patients with a predominant trabecular pattern (43%) did particularly poorly. Although sex was significantly associated with survival using a univariate analysis, this effect disappeared in a multivariate Cox model that adjusted simultaneously for other factors. CONCLUSION: This investigation suggests that histologic subtype and clinical features may provide useful prognostic information in hepatocellular carcinoma. Poorer survival was observed in males, older patients with poorly differentiated tumors, or when associated with cirrhosis. Age younger than 45 years was a good prognostic factor, and presence of cirrhosis had an adverse effect on survival.

Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: ten-year analysis--an intergroup study.

PURPOSE: Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients. This report updates the analysis of the high-risk group and reports the results of the low-risk group. METHODS: Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured > or = 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy. RESULTS: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group (P=.0006 for DFS and P=.02 for OS). Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51 % (P=.0009) and OS of 75% versus 65% (P=.06). Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group. CONCLUSION: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free state and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group.

A randomized study of radiotherapy alone versus radiotherapy plus 5-fluorouracil and platinum in patients with inoperable, locally advanced squamous cancer of the esophagus.

Squamous cell cancer of the esophagus is the most common cancer among black South African males, and 60% of patients present with localized inoperable disease. Combined chemoradiotherapy has been reported to be superior to radiotherapy alone for localized inoperable esophageal cancer in North American patients. A study was carried out to determine if this was also applicable to South African patients, who present with more advanced disease. From September 1991 through June 1995, 70 patients with locally advanced (T3N0-1M0) squamous cancer of the esophagus were prospectively randomized to receive radiotherapy alone or radiotherapy combined with cisplatin and 5-fluorouracil. There was no statistically significant survival difference between the two groups. The median survival was 144 days in the group receiving radiotherapy alone, and 170 days in the group receiving radiotherapy combined with chemotherapy (p = 0.42). The degree of weight loss before initiation of therapy had a significant effect on survival regardless of the treatment arm. Radiotherapy in combination with chemotherapy, as administered in this study for South African patients with locally advanced, inoperable squamous cancer of the esophagus, is no better than radiotherapy alone.

Fadrozole versus megestrol acetate: a double-blind randomised trial in advanced breast cancer.

Ninety-six patients were entered into a randomised, double-blind, double-dummy, clinical trial to assess the efficacy and safety of fadrozole as compared to megestrol acetate as second-line hormonal treatment for patients with advanced breast cancer. Analysis of results was on an intention-to-treat basis and included response rate, time to progression (TTP), time to treatment failure (TTF) and survival. Forty-six patients received fadrozole and 50 were randomised to megestrol acetate. Patients and pretreatment prognostic variables were balanced in the two arms of the trial. The objective response rates [3/46 (7%) for fadrozole and 3/50 (6%) for megestrol acetate], TTP, TTF and survival were similar in the two arms of the trial. Toxicity was also similar in the two arms of the trial and consisted mainly of oedema, hypertension and minor gastrointestinal symptoms. Fadrozole appears to be as active as megestrol acetate in second-line hormonal treatment of advanced breast cancer.

Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment.

PURPOSE: To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). PATIENTS AND METHODS: One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. RESULTS: Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models. CONCLUSION: There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.

Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

PURPOSE: To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer.

Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.

The low-grade lymphoproliferative disorders.

Rapid advances in our understanding of the biology and pathology of lymphoproliferative disorders, permitted mainly by new diagnostic tools, constantly change our approach to this heterogenous group of disorders. In this review of the more indolent subgroup of lymphoproliferative disorders, some of the recent advances are highlighted, and treatment options discussed.

The role of radiotherapy in the management of operable locally advanced breast carcinoma: results of a randomized trial by the Eastern Cooperative Oncology Group.

BACKGROUND: The purpose of this study was to test the role of radiotherapy following total mastectomy, axillary dissection, and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma. METHODS: After undergoing mastectomy and axillary dissection, 426 patients with locally advanced breast carcinoma were registered on study and stratified by patient characteristics and risk factors. All patients were then treated with six courses of chemohormonotherapy. After being restaged, the 332 patients remaining without recurrence were randomized to receive prophylactic radiotherapy or to undergo observation and receive radiotherapy only if and when there was locoregional recurrence. RESULTS: Three hundred twelve of 332 randomized patients were deemed eligible and analyzed for both time to relapse and survival. The median follow-up period was 9.1 years. There were no significant differences in time to relapse and overall survival between the two treatment arms. Of those assigned to radiation, 60% relapsed, with a median time to relapse of 4.7 years, and 46% were alive at last follow-up, with a median survival of 8.3 years. Of those assigned to observation, 56% relapsed, with a median time to relapse of 5.2 years, and 47% were alive at last follow-up, with a median survival of 8.1 years. The two treatment arms had significantly different patterns of sites of first recurrence. There were 9% fewer locoregional first recurrences among those assigned to radiation than among those assigned to observation (15% vs. 24%), whereas there were 15% more first relapses at distant sites (50% vs. 35%) among those assigned to radiation (P = 0.003). CONCLUSIONS: Radiotherapy for locally advanced breast carcinoma, following mastectomy, axillary dissection, and adjuvant systemic therapy, results in fewer locoregional but more distant recurrences at first relapse. No significant advantage was seen for consolidation radiotherapy over observation in terms of either time to relapse or survival, both of which were virtually identical in the two treatment arms. [See editorial counterpoint on pages 1061-6 and reply to counterpoint on pages 1067-8, this issue.]

Cisplatin versus cisplatin plus D-Trp-6-LHRH in the treatment of ovarian cancer: a pilot trial to investigate the effect of the addition of a GnRH analogue to cisplatin.

Thirty-four patients with histologically confirmed ovarian cancer were entered into a pilot study. Patients were randomized to receive cisplatin alone or cisplatin plus D-Trp-6-LHRH(decapeptyl). Objective response (complete and partial response) was documented in 9 of 14 patients on cisplatin and in 12 of 18 patients on cisplatin plus decapeptyl. Median time to treatment failure and median survival times were the same in the two treatment regimens. Toxicities were similar in the two treatment arms, except for hot flashes which only occurred in patients on cisplatin plus decapeptyl.

A phase II trial of fludarabine in patients with previously treated chronic lymphocytic leukaemia.

OBJECTIVES: To evaluate fludarabine in patients with chronic lymphocytic leukaemia (CLL) not responding to standard treatment. DESIGN SETTING: Fludarabine was administered for 5 consecutive days and repeated 4-weekly. SUBJECTS: Seventeen patients at a single institution were treated. OUTCOME MEASURES: Objective remission was seen in 11 patients. The median survival time was 356 days. RESULTS AND CONCLUSIONS: Fludarabine is an effective treatment for patients with advanced CLL.

13-Cis-retinoic acid and interferon alpha-2a in patients with advanced esophageal cancer: a phase II trial.

The aim of this study was to investigate the possible therapeutic effect of 13-cis-retinoic acid plus interferon alpha-2a in patients with inoperable squamous cancer of the esophagus. Patients with advanced, measurable, histologically confirmed squamous carcinoma of the esophagus with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 who had adequate bone marrow, liver, and renal function were eligible for study. Patients were given cis-retinoic acid 1 mg/kg/day per mouth continuously and interferon alpha-2a 3 Mu/day for 3 days followed by 6 Mu subcutaneously daily thereafter. Seventeen patients were entered on study. Fifteen patients were evaluable for toxicity. The most common toxicities were grade 1 and 2 cheilitis, dry skin and flu-like symptoms which occurred in all patients. Two patients had grade 3 toxicity (1 anorexia and 1 fatigue). No grade 4 toxicity occurred. Fifteen patients were evaluable for response. No objective response was documented. The median survival time was 15 weeks. With no response seen it is unlikely that the combination of treatment as used in this study will be of benefit in patients with advanced squamous cancer of the esophagus.