Current landscape of ESMO/ASCO Global Curriculum adoption and medical oncology recognition: a global survey.

BACKGROUND: With the implementation of multidisciplinary treatment and development of multiple novel anticancer drugs in parallel with expanding knowledge of supportive and palliative care, a need for separate training and specialisation in medical oncology emerged. A Global Curriculum (GC) in medical oncology, developed and updated by a joint European Society for Medical Oncology/American Society of Clinical Oncology (ESMO/ASCO) GC Task Force/Working Group (GC WG), greatly contributed to the recognition of medical oncology worldwide. MATERIAL AND METHODS: ESMO/ASCO GC WG carried out a global survey on medical oncology recognition and GC adoption in 2019. RESULTS: Based on our survey, medical oncology is recognised as a separate specialty or sub-specialty in 47/62 (75%) countries participating in the survey; with a great majority of them (39/47, 83%) recognising medical oncology as a standalone specialty. Additionally, in 9 of 62 (15%) countries, medical oncology is trained together with haematology as a specialty in haemato-oncology or together with radiotherapy as a specialty in clinical oncology. As many as two-thirds of the responding countries reported that the ESMO/ASCO GC has been either fully or partially adopted or adapted in their curriculum. It has been adopted in a vast majority of countries with established training in medical oncology (28/41; 68%) and adapted in 12 countries with mixed training in haemato-oncology, clinical oncology or other specialty responsible for training on systemic anticancer treatment. CONCLUSIONS: With 75% of participating countries reporting medical oncology as a separate specialty or sub-specialty and as high as 68% of them reporting on GC adoption, the results of our survey on global landscape are reassuring. Despite a lack of data for some regions, this survey represents the most comprehensive and up-to-date information about recognition of medical oncology and GC adoption worldwide and will allow both societies to further improve the dissemination of the GC and global recognition of medical oncology, thus contributing to better cancer care worldwide.

Clinical outcomes in elderly patients with advanced non-small cell lung cancer: results from ARIES, a bevacizumab observational cohort study.

AIMS: Retrospective analyses from first-line clinical studies in advanced non-small cell lung cancer (NSCLC) have reported conflicting results on progression-free survival (PFS) and overall survival benefits with the addition of bevacizumab to chemotherapy in elderly patients. Here we report effectiveness and safety outcomes by age subgroup for patients with NSCLC in the ARIES observational cohort study. MATERIALS AND METHODS: ARIES enrolled patients with advanced non-squamous NSCLC who received first-line bevacizumab-containing treatment per physician's choice. Kaplan-Meier estimates were used to calculate medians and 95% confidence intervals for PFS and overall survival for patients aged <65, ≥65, <75 and ≥75 years. RESULTS: In total, 1967 patients receiving first-line treatment with bevacizumab and chemotherapy were enrolled. The median PFS and overall survival values were 6.4 (95% confidence interval = 6.0-6.8) and 14.2 (95% confidence interval = 12.7-15.2) months for patients aged <65 years, respectively, and 6.8 (95% confidence interval = 6.3-7.0) and 12.1 (95% confidence interval = 11.4-13.1) months for patients ≥65 years, respectively. For patients <75 years, the median PFS and overall survival values were 6.6 (95% confidence interval = 6.3-6.9) and 13.5 (95% confidence interval = 12.6-14.5) months, respectively, and 6.6 (95% confidence interval = 5.9-7.1) and 11.6 (95% confidence interval = 10.0-12.5) months, respectively, for patients ≥75 years. Incidence proportions of bevacizumab-associated adverse events were generally similar across all age groups. CONCLUSIONS: Data from the ARIES study suggest that treatment with bevacizumab in combination with chemotherapy is a viable first-line treatment option for elderly bevacizumab-eligible patients with advanced non-squamous NSCLC.

High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631.

Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.

Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations.

BACKGROUND: Merkel cell carcinoma is a primary small blue cell tumor of the skin with a proclivity to metastasize. Surgery and radiation therapy have defined roles in the primary treatment of Merkel cell carcinoma. Systemic chemotherapy can produce good response rates but does not have a primary role in the management of nondisseminated Merkel cell carcinoma patients. METHODS: Twenty-two patients were identified over the last 10 years in a retrospective analysis of tumor registries from the 6 hospitals of the ScrippsHealth facilities. Hospital and clinic charts as well as pathology specimens were reviewed. RESULTS: Eight patients underwent Mohs' surgery with permanent tissue technique. None of these patients had a subsequent local recurrence. Six patients received adjuvant radiation therapy, only one of whom developed a disease recurrence within a radiation port. Systemic chemotherapy was given to seven patients. One patient did not accept further treatment after a punch biopsy. CONCLUSIONS: Merkel cell carcinoma is an aggressive primary neoplasm of the skin, the histologic diagnosis of which can be difficult. Mohs' surgical technique combined with radiation therapy provides excellent local control. Systemic treatment is associated with high response rates, but to the authors' knowledge durable responses are uncommon.

Is quality of life predictive of the survival of patients with advanced nonsmall cell lung carcinoma?

BACKGROUND: Several studies have recently reported on the importance of quality of life (QOL) in predicting the survival of patients with lung carcinoma. To confirm these reports, the relationship between survival and QOL, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and Duke-UNC Social Support Scale, was examined within a group of 206 patients with advanced nonsmall cell lung carcinoma treated in a randomized clinical trial conducted by the Cancer and Leukemia Group B (CALGB 8931). METHODS: Patients completed the EORTC instrument and the Duke-UNC Social Support Scale at baseline in the clinic. The Cox proportional hazards model was used to determine the incremental contribution QOL provided in predicting survival beyond the effect of known clinical prognostic variables. RESULTS: Clinical factors that were jointly predictive of poorer survival included low performance status, nonadenocarcinoma histology, presence of dyspnea, weight loss greater than 5%, albumin level less than 3.5 mg/dL, and adrenal metastases. Univariate analyses showed that patient-reported EORTC subscales describing increased pain, appetite loss, fatigue, lung carcinoma symptoms, poorer overall QOL, and poorer physical functioning predicted significantly poorer survival. Multivariate analyses showed that, after adjustment for clinical factors, overall QOL was not a significant predictor of survival. Rather, the only EORTC subscale of prognostic importance was the pain subscale, in which a 40-point increase was associated with a 27% increase in the hazard rate. CONCLUSIONS: This study did not confirm the prognostic importance of overall QOL. Rather, after adjustment for significant clinical factors, a patient-provided pain report had the greatest prognostic importance.

An all oral antiemetic regimen for patients undergoing high-dose chemotherapy with peripheral blood stem cell transplant.

The purpose of the study was to assess the toxicity and efficacy of an oral, combination antiemetic regimen including granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) in the setting of highly emetogenic conditioning chemotherapy for stem cell transplantation. Antiemetic prophylaxis consisted of oral granisetron 2 mg once daily, oral prochlorperazine 10 mg q 6 h and oral dexamethasone 4 mg q 6 h, beginning 1 h prior to chemotherapy on each of the 4 days of chemotherapy and continuing until 24 h after the completion of high-dose chemotherapy (HDC). Patients received either CVP (cyclophosphamide 6 g/m2, VP-16 1800 mg/m2 and carboplatin 1200 mg/m2) or CTP (thiotepa 500 mg/m2 in place of VP-16) in four daily doses given over 4 h from days -4 to -1. Previously mobilized and cryopreserved peripheral blood stem cells (PBSC) were reinfused on day +1. Evaluation of nausea, emetic episodes (EE), adverse events, and rescue medications were recorded on a daily patient diary. Thirty-six patients were entered. Fifty-three percent (95% CI = 37-75%) of patients achieved complete response for emesis (CR = 0 EE/24 h) and 75% (95% CI = 58-90%) had combined complete and major response (CR+MR = 0-3 EE/24 h) during all 5 of the treatment days. During the 5 study days, the average number of patient-days with no emesis was 3.7 (74%) and with 1-3 EE was 4.3 (86%). On days -4, -3, -2, -1 and 0, the combined CR+MR rate for emesis was 97, 92, 86, 78 and 75%, respectively. Nausea was absent or mild on all 5 study days in 57% (95% CI = 37-75%). Eight patients had severe late-onset emesis occurring on days +1 to +3 after reinfusion of stem cells. No clinically significant toxicities attributable to the antiemetic regimen were observed. An all oral antiemetic regimen of granisetron, prochlorperazine and dexamethasone appears to be safe and highly effective in patients receiving multiple, daily, high-dose chemotherapy regimens. This regimen offers the advantage of cost-savings, a low side-effect profile and ease of administration in the predominately outpatient setting of HDC with peripheral blood stem cell transplant (PBSCT).

A longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931.

A quality of life (QOL) endpoint supplemented standard clinical endpoints of survival, tumor response, and toxicity in a double-blind study conducted by the Cancer and Leukemia Group B (CALGB) where 291 patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive cisplatin/vinblastine with either hydrazine sulfate (HS) or placebo. The difficulties associated with the analysis of the longitudinal QOL data, and the contributions that the QOL endpoint made to the understanding of treatment differences, will be the focus of this paper.

Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies.

PURPOSE: A prospective study to determine the feasibility of high-dose chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient setting. METHODS: One hundred thirteen consecutive patients underwent 165 cycles of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific. Initially, patients were hospitalized for HDC, discharged on completion, and maintained as outpatients unless toxicities required rehospitalization (subtotal outpatient transplantation [STOT]). Once this was established as safe, a total outpatient transplant (TOT) program was developed in which patients received all of the HDC, as well as supportive care, as outpatients. Patients who declined the outpatient programs received the same HDC and supportive care as inpatients. RESULTS: In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of the outpatient transplant programs. Five patients in the STOT program could not be discharged from the hospital because of toxicities that developed during HDC; thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were never readmitted. The mean +/- SEM total hospital length of stay (LOS), including all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001). One treatment-related death occurred in each treatment setting: day 120 inpatient, day 17 STOT, and day 110 TOT. CONCLUSION: Outpatient management of HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT program resulted in significant reduction in hospital LOS, while the TOT program appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is unnecessary in most patients.

Cladribine and mitoxantrone dose escalation in indolent non-Hodgkin's lymphoma.

PURPOSE: Since cladribine (2-chlorodeoxyadenosine [2-CdA]) and mitoxantrone both exhibit major activity against indolent lymphoid malignancies and have different mechanisms of action, we performed a dose-escalation study of 2-CdA and mitoxantrone in patients with alkylator-failed indolent lymphoma to determine the maximum-tolerated dose (MTD) of this combination and to make preliminary observations about efficacy. PATIENTS AND METHODS: Twenty-three patients were treated every 28 to 35 days, in cohorts of at least three patients, with stepwise dose escalations until dose-limiting toxicities (DLTs) were encountered. The initial dose levels were 2-CdA 0.1 mg/kg/d by continuous infusion for 7 days, mitoxantrone 5 mg/m2 intravenously (i.v.) on day 1, and prednisone 100 mg/d on days 1 to 5. Mitoxantrone was dose-escalated in increments of 2.5 mg/m2 i.v. on day 1. RESULTS: The MTD of the combination was 2-CdA 0.1 mg/kg/d for 7 days, mitoxantrone 7.5 mg/m2 i.v. on day 1, and prednisone 100 mg/d on days 1 to 5. Myelosuppression and infection were the DLTs. The recommended phase II doses were 2-CdA 0.075 mg/kg/d for 7 days mitoxantrone 5 mg/m2 i.v. on day 1; prednisone was omitted to decrease the risk of opportunistic infections. The overall response rate was 70%, with 22% complete responses (CRs) and 48% partial responses (PRs). The median duration of CR was 15 months and PR 5 months. CONCLUSION: These results demonstrate the feasibility and safety of combining 2-CdA and mitoxantrone in the treatment of indolent lymphoma, and appear to confirm clinically the mechanistic synergism and rationale for this combination regimen. Prednisone exacerbated the risk of opportunistic infection and was omitted. The overall response rate was high, including durable CRs. Further studies of this combination regimen are warranted in untreated and alkylator-failed indolent lymphoma.

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy.

PURPOSE: This study was designed to evaluate the absolute bioavailability (F value) of 2-chlorodeoxyadenosine (cladribine; 2-CdA) after multiple oral administrations, and the intersubject variability after oral and 2-hour intravenous (IV) administration schedules in patients with malignancy. PATIENTS AND METHODS: Patients with advanced malignancies were eligible. There were two treatment cycles; during cycle 1, patients received 2-CdA solution at 0.28 mg/kg/d orally under fasting conditions for 5 consecutive days concomitantly with omeprazole, and 4 weeks later during cycle 2 patients received 2-CdA as a 2-hour IV infusion of 0.14 mg/kg/d for 5 consecutive days. Serial blood samples for 2-CdA plasma levels were obtained after drug administrations on days 1 and 5 during each treatment cycle. RESULTS: Ten patients completed cycles 1 and 2. The F value of oral 2-CdA measured on days 1 and 5 was 37.2% and 36.7%, respectively. For both oral and IV multiple administrations, there was no significant accumulation in maximum concentration (Cmax), and the intersubject variabilities (coefficient of variation [CV], approximately 40%) in Cmax and area under the concentration-time curve from 0 to 24 hours [AUC(0-24)] values were comparable for both routes on days 1 and 5. A three-compartment open model was applied to the plasma concentration data after oral and IV administrations and resulted in good agreement between observed and simulated concentration-time profiles. Neutropenia was the principal adverse event observed when 2-CdA was administered orally and IV. CONCLUSION: The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

Two unusual presentations of müllerian adenosarcoma: case reports, literature review, and treatment considerations.

Müllerian adenosarcomas of the uterus usually present as pedunculated endometrial masses in postmenopausal women with vaginal bleeding. Extraendometrial variants (originating in the ovary, adnexa, or myometrium) are much less common, and they tend to present at a more advanced stage due to their location. The sarcomatous portion of müllerian adenosarcoma can vary from low grade to very high grade and the clinical behavior of the tumors can be indolent or aggressive. We present two cases, one of which originated in the adnexa and the other in an apparent focus of uterine adenomyosis. These cases illustrate the difficulty of correct diagnosis and treatment.

Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.

PURPOSE: To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS: Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS: Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION: With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.

Prolactin-secreting pituitary carcinoma with implants in the cheek pouch and metastases to the ovaries. A case report and literature review.

BACKGROUND: Prolactin-secreting pituitary carcinomas are uncommon, locally destructive neoplasms that rarely metastasize outside the central nervous system. The authors report a case of a prolactin-secreting tumor that initially presented as the empty sella syndrome. Two recurrences along transsphenoidal surgery tracts in cheek pouches were followed by distant metastases later in the abdomen and pelvis. Only 10 previous cases of either extracranial or intracranial metastases from prolactin-secreting pituitary carcinomas have been reported. No metastases below the diaphragm have been reported previously. METHODS: The patient's cheek pouch implants, lymph node metastases, ovarian metastases, and uterine metastases were studied with prolactin-specific immunohistochemistry. RESULTS: Long term treatment with bromocriptine, several debulking surgeries, extensive local radiation therapy (external beam and proton beam), and cytotoxic chemotherapy had little impact. Tamoxifen, however, may have slowed tumor growth. CONCLUSION: Tamoxifen may have efficacy in the treatment of prolactin-secreting pituitary carcinomas.

2-Chlorodeoxyadenosine activity in patients with untreated, indolent non-Hodgkin's lymphoma.

Based on the encouraging results of the use of 2-chlorodeoxyadenosine ([2-CdA], cladribine) in patients with advanced, low-grade lymphomas resistant to conventional therapy and the acceptable toxicity profile encountered, we conducted a phase II trial of 2-CdA in patients with untreated indolent lymphomas. Twenty-eight patients with untreated low-grade lymphomas were given 2-CdA at 0.1 mg/kg/d as a 7-day continuous infusion every 28 to 35 days. A total of 89 courses, median of three courses per patient, of 2-CdA were administered. Seventeen men and 11 women with a median age of 58 years were treated. Fifteen patients had diffuse small lymphocytic (8 with plasmacytoid features), 10 had follicular small cleaved-cell, and there were single patients with monocytoid B-cell, mantle cell and mucosa-associated lymphoid tissue (MALT) lymphoma histologies. All 28 patients were evaluable for toxicity and 26 were evaluable for response. Nine (35%) patients (4 with diffuse small lymphocytic, 3 with follicular small cleaved-cell, 1 with mantle cell, and 1 with MALT lymphoma) achieved a complete response, and 14 (54%) patients (8 with diffuse small lymphocytic, 5 with follicular small cleaved-cell, and 1 with monocytoid B-cell lymphoma) achieved a partial response, for an overall response rate of 88%. The median response duration was 10 months (range, 3 to 44+). Myelosuppression was the principal toxicity. Actuarial survival at 60 months from initial diagnosis was 60% (95% confidence interval, 35% to 82%) and at 48 months from treatment onset was 62% (95% confidence interval, 39% to 83%). These results establish the major activity of 2-CdA in patients with untreated indolent lymphoma, especially those with the diffuse small lymphocytic subtype.

2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia.

PURPOSE: 2-chlorodeoxyadenosine (2-CdA; cladribine) is a purine analog with activity in patients with chronic lymphocytic leukemia (CLL) who fail to respond to alkylator therapy. We conducted a phase II trial of 2-CdA in previously untreated CLL patients. PATIENTS AND METHODS: 2-CdA was administered to 20 patients with previously untreated CLL as a 0.1-mg/kg/d 7-day continuous intravenous infusion every 28 to 35 days until maximum response or prohibitive toxicity. RESULTS: A median of four courses (range, one to nine) was administered to each patient. Five patients (25%) achieved a complete response and 12 (60%) achieved a partial response, for an overall response rate of 85%. The median response follow-up duration was 8+ months (range, 3 to 27). Myelosuppression was the principal toxicity. Four of 20 patients (20%) experienced grade III or IV thrombocytopenia. Three patients, all of whom received corticosteroid therapy, developed opportunistic infections at a median of 19 months following discontinuation of 2-CdA therapy. CONCLUSION: 2-CdA has major activity in patients with previously untreated CLL, and the lower response rates seen in previously treated patients may be due in part to poor marrow reserve from prior therapy. Determination of the relative effectiveness of 2-CdA, fludarabine, and chlorambucil in the treatment of CLL patients will require a randomized trial.

Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma.

The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.

Nonoperative management of non-small cell lung cancer: the current cancer and leukemia group B experience.

The Cancer and Leukemia Group B (CALGB) is studying nonoperative management in two subgroups of patients with advanced non-small cell lung cancer. In patients with regional disease, primarily those with bulky N2 or T4 disease or those with contralateral mediastinal involvement (N3), a phase III trial is under way to explore concurrent carboplatin as intensification of local therapy and additional systemic treatment. This builds on prior CALGB work demonstrating the benefits of induction chemotherapy prior to radiation for selected patients with stage III disease. For patients with still more advanced disease, a trial evaluating efficacy and cost of two supportive care modalities during intensive chemotherapy is about to begin accrual. Following its completion, the CALGB plans to evaluate new chemotherapy combinations based on one or more of the exciting new agents now being tested for the nonoperative management of non-small cell lung cancer.

Complete hematologic remissions in chronic-phase, Philadelphia-chromosome-positive, chronic myelogenous leukemia after 2-chlorodeoxyadenosine.

BACKGROUND: 2-Chlorodeoxyadenosine (Cladribine, Leustatin, Ortho Biotech, Raritan, NJ) (2-CdA) is a purine analog with activity in the treatment of lymphoid neoplasms. Interferon induces cytogenetic remissions in chronic myeloid leukemia (CML) and partial remissions in hairy cell leukemia, a disorder in which single courses of 2-CdA induce complete remissions. In vitro clonal growth of immature myeloid progenitors from normal marrow is markedly inhibited by 2-CdA. METHODS: 2-CdA was administered to 12 patients with Philadelphia-chromosome-positive CML, 11 chronic phase, and 1 accelerated phase, at 0.1 mg/kg/day by continuous intravenous infusion for 7 days every 28-35 days, until maximum peripheral hematologic response. RESULTS: Of 12 patients, 10 (83%) achieved complete hematologic responses and 2 (17%) partial hematologic responses after a median of two courses of 2-CdA. The median first hematologic response duration was 3 months. Of the seven patients who relapsed and were retreated with a median of two further courses of 2-CdA, five obtained responses (four complete and one partial) and two did not respond. The median second hematologic response duration was 4 months. No patient had significant Philadelphia-chromosome suppression. Reversible myelosuppression and severe cumulative T-cell immunosuppression associated with opportunistic infections in four patients were the principal toxicities. CONCLUSIONS: 2-CdA is active in CML, inducing complete hematologic responses, but the absence of cytogenetic responses and severe immunosuppression may limit its clinical use.