A 52-year-old dentist with kappa light chain multiple myeloma relapsed 6 months after 180 mg/m2 melphalan and an autograft. A partial remission had been attained after the autograft. Relapse occurred while he was on dexamethasone maintenance therapy. Chemotherapy was not an option due to low blood counts. Thalidomide was administered at relatively high doses (escalated up to 700 mg daily and continued for 4 months). There was a prompt decline in urine protein from 6067 mg/day to 2177 mg/day within a month. The response continued to improve with achievement of near-complete remission within 6 months and a decline in urine protein to 413 mg/day. Subsequently, grade 3 neutropenia and peripheral neuropathy required dose reduction to 200 mg/day. Disease activity parameters continued to improve on the lower dose of thalidomide. Nine months after starting thalidomide, the patient is in near-complete remission, enjoys an excellent quality of life, and has returned to work. We conclude that thalidomide can effectively control myeloma relapsing after high-dose chemotherapy, and may be especially useful in resistant cases or those unable to tolerate further chemotherapy.

Background: The prognosis of platinum resistant ovarian cancer is very poor and the treatment of choice has not been clearly defined. Patients and methods: We conducted a phase II study with the combination of ifosfamide i.v. at 2.25 g/m2 (days 1, 2) and etoposide per os at 100 mg daily (days 1- 10) every four weeks. To be eligible for the study patients had to be resistant to platinum and paclitaxel pretreated. Results: Forty-one patients entered the study. The median interval from the previous chemotherapy was 3.9 months. The median number of previous chemotherapeutic regimens was 2. Severe toxicities included neutropenia (41% of patients), leukopenia (29%) and thrombocytopenia (13%). Thirty-five patients are assessable for response. Nine patients responded (22% of the eligible, 26% of the assessable), four of them demonstrated complete response to chemotherapy (10% and 12%, respectively), while three patients demonstrated stabilization of their progressive disease. After a median follow-up of 18 months, time to progression is 3 months (range 0.9-14.4), duration of response is 9 months (2.5-11) and median survival is 13 months (2.5-37.4+). Conclusions: The combination of ifosfamide with oral etoposide appears to have significant but manageable toxicity and encouraging efficacy in platinum resistant ovarian cancer.

We report a patient with a history of orchiectomy for Leydig cell tumor of the testis who developed Cushing syndrome. This syndrome was due to ectopic production of cortisol and was the primary feature of tumor recurrence. (C) 2000 Elsevier Science Inc.

Objectives. Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent carcinoma of the endometrium, and the combination of these two agents has shown activity in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity. Methods. Twenty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-h period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor (G-CSF) support. The chemotherapy was repeated every 3 weeks for a maximum of six courses. Results. Sixteen patients (67%; 95% confidence interval, 4584%) achieved an objective response, including seven complete responses and nine partial responses. The median duration of response was 7 months, and the median times to progression and survival for all patients were 8.4 and 17.6 months, respectively. Some degree of neurotoxicity occurred in 44% of patients. Grade 3 or 4 toxicity included granulocytopenia in 22% of patients and peripheral neuropathy in 9%. Conclusion. The combination of paclitaxel with cisplatin with G-CSF support appears active in patients with metastatic or recurrent carcinoma of the endometrium. The significant incidence of neurotoxicity is of concern and alternative methods of administration of the two agents could be evaluated. (C) 2000 Academic Press.

Testicular non-Hodgkin's lymphoma is an uncommon disease and its outcome following chemotherapy and/or radiotherapy has been variable. A retrospective analysis was performed on 26 patients with primary testicular lymphoma treated predominantly with anthracycline-based chemotherapy between 1984 and 1999. The patients' median age was 60 years (range 19-82 years) with 17 (65.4%) patients being older than 60 years. Four (15.4%) patients had constitutional B symptoms. There were 11 (42.3%) patients with high grade lymphoma, 12 (46.2%) with intermediate grade, 1 (3.8%) with low grade and 2 (7.7%) were not classified. According to the Ann-Anbor staging system, 18 patients (69.2%) had early (stage I/II) and 8 (30.8%) advanced (stage III/IV) disease. Chemotherapy was administered to 24 patients including 22 patients who received anthracycline-based chemotherapy. Two stage IEA patients were treated with orchidectomy and adjuvant radiotherapy to the regional lymph nodes without systemic chemotherapy. Chemotherapy alone resulted in a complete remission (CR) in 14 (58.3%) of 24 patients and partial remission in 1 (4.2%), amounting to an overall response rate (RR) of 62.5%. Of the 5 stage I patients who had chemotherapy on an adjuvant basis, 4 (80%) had CR/no evidence of disease. Of the 11 stage II patients, 8 (72.7%) achieved CR and 1 (9.1%) PR (overall RR of 81.8%). CR was obtained in 2 (25%) of 8 stage III/IV patients. Both patients remain disease free for 26 and 65 months. Excluding the 5 stage I patients, chemotherapy resulted in a CR in 10/19 (52.6%) patients and a PR in 1/19 (5.2%), inducing an overall RR of 57.8%. The mean duration of response was 75 months (range 8-145.5+ months). After a median follow-up of 87 months (range 0.13-145.5+ months) the median survival time was 31 months (range 0.13-145.5+ months) and the median time to progression (TTP) 17 months (range 0.13-145.5+ months). The median TTP was significantly higher in early disease compared to that of advanced disease (52 vs. 3 months, p = 0.02). Of the 3 patients who relapsed following disease-free status, CNS involvement occurred in 2 stage II patients and contralateral testis involvement in 1 stage IEA, respectively. The latter remained disease free for 2 years following orchidectomy alone. The other 2 patients who relapsed did not respond to salvage chemotherapy and died. There was no significant relationship between the values of LDH and β2-microglobulin with the outcome except for ESR which was significantly related with the CR (p = 0.005) or RR (p = 0.005). In conclusion, patients with primary testicular lymphoma have a poor outcome, despite the treatment with anthracycline-containing regimens. Treatment with anthracycline-based chemotherapy is recommended in patients at early stages. In advanced disease, more intensive or investigational regimens should be considered. Because the relapse rate in the CNS and contralateral testis is quite high in most studies, prophylactic CNS treatment and radiotherapy to the other testis should be included in the management of testicular lymphoma. Copyright (C) 2000 S. Karger AG, Basel.

Gemcitabine plus paclitaxel and paclitaxel plus carboplatin are active and well tolerated in patients with advanced non-small cell lung cancer, showing similar rates of response and survival. The Hellenic Cooperative Oncology Group conducted a randomized phase III trial comparing gemcitabine plus paclitaxel with paclitaxel plus carboplatin. Patients were randomly assigned to two groups. Group A received paclitaxel 200 mg/m2 plus carboplatin (area under the curve = 6) on day I. Group B received paclitaxel in identical fashion to group A plus gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks. A minimum of two cycles and a maximum of six cycles was allowed. To date, 127 eligible patients (63 in group A and 64 in group B) have been randomized; the median follow-up time is 4.6 months. Preliminary results suggest that both combinations can be given in full doses and are well tolerated. Grade 3/4 neutropenia was mild but more prominent in group A (10% v 3%, respectively) while thrombocytopenia was not significant for either group. Moreover, severe neurotoxicity, hepatotoxicity, or cardiac toxicity has not been observed in the vast majority of patients in either group. Although patients in group B experienced higher response rates (37.5%) than those in group A (21.8%), the difference between the groups was not statistically significant. Definite conclusions about this study cannot be made until more data are available. Copyright (C) 2000 by W.B. Saunders Company.

Purpose: To review the clinical features, complications, and treatment of Waldenstrom's macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. Methods: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. Results: The clinical manifestations associated with Waldenstrom's macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. Conclusion: Waldenstrom's macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients' survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent.

High-dose chemotherapy with autologous peripheral blood progenitor cell (PBPC) support has become a widely used treatment strategy. In order to simplify the procedure, a single very large-volume leukapheresis, programme combined with short-term refrigerated storage of the PBPC was developed. Seventy-two patients suffering from various relatively chemosensitive malignancies received high-dose chemotherapy, consisting of agents with short in vivo half-lives and 24 to 48 hours later, the refrigerated PBPC were reinfused. A single very large-volume apheresis was sufficient to obtain at least 2 × 106/kg CD34+ cells in 58 patients, (81%). and 63% had at least 2.5 × 106 CD34+ cells/kg. Only two patients (3%) were transplanted with less than 1 × 10 CD34+ cells/kg. In three patients (4%) leukupheresis was repeated because of insufficient number of PBPC. The median CD34+ cell count was 3 × 106/kg. A median of 38.5 L blood (range, 21 to 59) was processed, which accounted for a median of 9 × patient's total blood volume. Very large-volume leukapharesis was well tolerated with symptomatic hypocalcemia being the most common (18%) side-effect. The median time to neutrophils >1.5 × 109/L, and to self-supporting platelet COUDI >25 × 109/L, was 10 and 12 days after reinfusion of PBPC graft, respectively. There were no treatment-related deaths. Our results indicate that this simplified approach of PBPC transplantation can be associated with prompt hematologic recovery in most patients and that it can be useful in settings where facilities are limited or for certain diseases where conditioning regimens with short hall-life are appropriate. © 2000 Wiley-Liss, Inc.

Multiple myeloma (MM) is a B-cell neoplasm characterized by bone marrow infiltration with malignant plasma cells, which synthesize and secrete monoclonal immunoglobulin (Ig) fragments. Despite the considerable progress in the understanding of MM biology, the molecular basis of the disease remains elusive. The initial transformation is thought to occur in a post-germinal center B-lineage cell, carrying a somatically hypermutated Ig heavy chain (IGH) gene. This plasmablastic precursor cell colonizes the bone marrow, propagates clonally and differentiates into a slowly proliferating myeloma cell population, all under the influence of specific cell adhesion molecules and cytokines. Production of interleukin-6 by stromal cells, osteoblasts and, in some cases, neoplastic cells is an essential element of myeloma cell growth, with the cytokine stimulus being delivered intracellularly via the Jack-STAT and ras signaling pathways. While karyotypic changes have been identified in up to 50% of MM patients, recent molecular cytogenetic techniques have revealed chromosomal abnormalities in the vast majority of examined cases. Translocations mostly involve illegal switch rearrangements of the IGH locus with various partner genes (CCND1, FGFR3, c-maf). Such events have been assigned a critical role in MM development. Mutations in coding and regulatory regions, as well as aberrant expression patterns of several oncogenes (c-myc, ras) and tumor suppressor genes (p16, p15) have been reported. Key regulators of programmed cell death (BCL-2, Fas), tumor expansion (metalloproteinases) and drug responsiveness (topoisomerase II alpha) have also been implicated in the pathogenesis of this hematologic malignancy. A tumorigenic role for human herpesvirus 8 (HHV8) was postulated recently, following the detection of viral sequences in bone marrow dendritic cells of MM patients. However, since several research groups were unable to confirm this observation, the role of HHV8 remains unclear. Translation of the advances in MM molecular biology into novel therapeutic strategies is essential in order to improve disease prognosis.

Non-African Burkitt's lymphoma is a rare disease among adults without AIDS. Among 1352 Greek adult patients with non-Hodgkin's lymphoma, 24 cases (1.8%) were classified as Burkitt's (BL) or Burkitt-like (BLL) lymphoma. Eleven cases fulfilled the criteria of BL and 13 of BLL. No statistical differences were found in the general characteristics of the two groups at the time of diagnosis. Extranodal involvement was a common finding in both groups and bulky disease (> 10 cm) was observed in almost one half of the patients. The majority of the patients were treated with intensive, although different, protocols. After induction treatment, complete remission (CR) was achieved in 14 patients (60.8%). CR was reached in all cases with stage I-II, while in stage IV the CR rate was 30.4%. The median overall survival was 27 months. The median survival for BL was 13 months compared to 27 months in the BLL group (P = 0.34). The data of the present retrospective analysis, indicated that there were not significant clinical differences between BL and BLL variants. Since BLL is still a non-reproducible category in the REAL classification, all BL variants must be treated uniformly with intensive protocols. (C) 2000 Elsevier Science Ltd.

In order to assess the role of α-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with α-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone. (C) 2000 Wiley-Liss, Inc.

BACKGROUND. The combination of paclitaxel with cisplatin or carboplatin has become the preferred chemotherapy regimen in the treatment of epithelial ovarian carcinoma. Anthracyclines also have activity in this disease. We conducted a Phase II study by using the combination of paclitaxel, cisplatin, and epirubicin for the treatment of advanced ovarian carcinoma. METHODS. Forty consecutive patients with optimally (n = 7) or suboptimally (n = 33) debulked advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV) were treated with paclitaxel, 135 mg/m2, as a 3-hour intravenous infusion, cisplatin 75 mg/m2 intravenously (i.v.), and epirubicin 50 mg/m2 i.v. every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was administered at a dose of 5 μg/kg/day on Days 5-9. RESULTS. Among 28 patients with measurable disease, 24 (86%%) achieved an objective response including 19 complete and 5 partial responses. Among 18 patients who underwent reassessment laparotomy, pathologic complete response was confirmed in 9 patients. At a minimum follow-up of 40 months, the median overall survival had not been reached whereas the median time to progression for all patients was 18.7 months. The median remission duration for women with measurable disease who responded to treatment was 14 months. The treatment was well tolerated without toxic deaths; the most common toxicity was Grade 3/4 neutropenia that occurred in 30% of patients. Significant neuropathy (Grade 2 or higher) developed in only 8% of patients. CONCLUSIONS. The combination of paclitaxel, cisplatin, and epirubicin is a well tolerated outpatient regimen with significant activity in the treatment of advanced epithelial ovarian carcinoma. (C) 2000 American Cancer society.

Background: Gemcitabine and vinorelbine have shown activity in breast cancer. A phase II trial was initiated in order to evaluate the response rate (RR) and time to progression (TTP) of the combination of the two drugs in patients with metastatic breast cancer progressing after first-line taxane-based chemotherapy. Patients and methods: Thirty-one patients were treated with the combination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine 30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. Results: Of 27 evaluable patients 1 (4%, 95% confidence interval (95% CI): 0.1%-19%) achieved complete remission (CR), five (18%; 95% CI: 6%-38%) partial remission (PR), eleven (40%; 95% CI: 22%-61%) stable disease and ten patients progressed. The median duration of response was six months (range 4-10+) and the median duration of disease stabilization was five months (range 2-22+). With a median follow-up of 16 months (range 0.4-22+) the median TTP was 3.5 months (range 0.4-22+) and the median survival was 9.5 months (range 0.4-22+). Grade 3-4 toxicities were granulocytopenia 15 patients (48%), rash 3 patients (10%), neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%). In conclusion the combination of gemcitabine/vinorelbine in the doses administered in this group of patients had a response rate of 22% and needs to be further evaluated in metastatic breast cancer.

Purpose: The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity, reasonable activity and easy outpatient administration. Purpose of our present prospective study was to evaluate the dose-response relationship of paclitaxel. Patients and methods: Since July 1996, 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial. Ninety nine patients (group A) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 (group B) to receive the same regimen with paclitaxel increased to 225 mg/m2. Eligibility criteria included WHO performance status 0-2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis, no prior chemotherapy and adequate renal and hepatic function. Patients in both groups were well-matched with baseline disease characteristics. Results: In group A with 90 evaluable patients, the response rate was 25.6%(6 CR, 17 PR) whereas in group B with 88 evaluable patients, the response rate was 31.8% (3 CR, 25 PR), P = 0.733. Median time to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months, P = 0.044). The median survival was 9.5 months for group A versus 11.4 months for group B (P = 0.16). The one-year survival was 37% for group A and 44% for group B (P = 0.35). The best prognostic factor for one-year survival was the response rate (P < 0.0001). With a relative dose intensity of paclitaxel 0.94 in both groups, neurotoxicity (P = 0.025) and leucopenia (P = 0.038) were more pronounced in group B patients. No toxic death was observed. Conclusions: Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia. The better response rate, the longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant.

Most patients with multiple myeloma (MM) present with symptoms, have evidence of generalized disease, and require chemotherapy promptly to reduce the malignant clone. Some patients present with a local symptom from a single plasmacytoma but no myeloma elsewhere. Such patients usually become free of symptoms after local radiotherapy. In patients with MM without symptoms, the diagnosis is made on the basis of screening laboratory tests. In patients with either solitary plasmacytoma of bone or asymptomatic MM, systemic treatment should be deferred until there is evidence of disease progression. (C) 2000 by The American Society of Hematology.

Recent data suggest that thalidomide is active in approximately 30% of patients (pts) with refractory multiple myeloma. Between 7/99 and 7/00 we treated 38 pts with refractory myeloma with thalidomide 200 mg PO q.h.s, increased to 400 mg after two weeks (in absence of severe side effects), and intermittent dexamethasone 40 mg p.o. x 4 days on days 1-4, 9-12, 17-20 followed by monthly dexamethasone (days 1-4). Pts median age was 67 years (49 to 79 years). Immediately prior therapy has consisted of high-dose pulse dexamethasone (21 pts) or VAD (17pts). Twelve pts had previously received an autologous stem cell transplant. Fourteen pts were considered as primary refractory and 24 pts were treated during refractory relapse. Serum b2-microglobulin > 3.0 mg/dl was present in 66% of pts and elevated serum LDH in 26%. Among the 33 patients évaluable for response so far, 17 (52%) have achieved a partial response defined by reductions > 50% of serum monoclonal protein and/or by >75% of urine monoclonal protein. The time to response was short (median: 1.5 months, range 0.5 to 3 months). Side effects included constipation (75%), morning somnolence (54%), tremor (25%), dry skin/rash (18%), headache (14%) and peripheral neuropathy (7%). Our results indicate activity of the combination of thalidomide with dexamethasone in pts with multiple myeloma refractory to dexamethasone-based regimens. Pts accrual and follow up is ongoing in order to define the activity of this combination in pts'subsets and to assess the duration of response.

The importance of insulin-like growth factor 1 (IGF-1) in human serum for the early diagnosis of prostate cancer is controversial. The IGF-1/PSA ratio may improve the performance of prostate specific antigen (PSA) as a prostate cancer marker. IGF-1, along with PSA and free PSA concentration, was measured in the serum of 34 patients with prostate cancer and in 131 patients with benign prostatic hyperplasia (BPH). Although IGF-1 concentration did not significantly differ between the groups, PSA/IGF-1 ratio could clearly distinguish the two groups. In patients with cancer but not in patients with BPH, IGF-1 concentration correlated with PSA and free PSA. The values of PSA and free PSA correlated with each other for both groups. Receivers Operating Curve (ROC) analysis indicated a better sensitivity to specificity ratio for PSA/IGF-1 than for PSA or Free/Total (F/T) PSA.

Among all imaging modalities, magnetic resonance imaging provides the most useful information about the accurate staging of solitary bone plasmacytoma, the prediction of progression of asymptomatic multiple myeloma and the prognosis of symptomatic multiple myeloma. Furthermore, magnetic resonance imaging contributes to the differential diagnosis of compression fractures in patients with myeloma and can be used for assessment of response to treatment.

Preliminary evidence suggests that rituximab, a chimeric antibody that targets CD20+ B cells, may be active in Waldenstrom's macroglobulinemia (WM). In May 1999 we initiated a prospective trial during which patients with WM were treated with rituximab, 375 mg/m2, administered by IV infusion weekly for 4 consecutive weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. Twelve patients have been treated so far.Eight patients were previously untreated, 2 primary refractory and 2 were treated during resistant relapse. The median age was 77 years (range: 39 to 85 years), hemoglobin was < 10.0 gr/ dl in 5 patients, lymphadenopathy and splenomegaly were present in 6 and 5 patients respectively. After the initial 4-week courses of rituximab responses were as follows: 75% reduction of IgM in 3 patients, 50% reduction of IgM in 2 patients, 25% reduction of IgM in 1 patient, stable disease in 4 patients and progressive disease in 2 patients. At least 50% reduction of IgM was noted in 3 of 8 previously untreated patients and in 2 of 4 pretreated patients. Among the 10 patients eligible for the second 4-week course of rituximab, 5 patients are évaluable so far: a 25% decrease of IgM was noted in two patients with stable disease after the first course of rituximab. Disappearance or significant reduction of lymphadenopathy or splenomegaly and of bone marrow lymphocytosis occurred in all responding patients. Treatment with rituximab was well tolerated: 3 patients developed grade 1,2 rigors and fever and 2 patients developed flushing. Our prospective study indicate that rituximab is an active and well torelated agent for the treatment of WM.

Five cases of acute neutropenic enterocolitis complicating taxane-based chemotherapy are described. During a 34-month period, our department administered 4,600 courses of taxane-based (paclitaxel and docetaxel) chemotherapy to 800 cancer patients. Seven to 10 days postchemotherapy in five patients (0.1% of the given courses), neutropenic fever, abdominal pain, rebound tenderness, and grade II-IV diarrhea (bloody in two cases) developed. Two patients had oral candidiasis, and in two others septic shock developed. Computed tomography scans of the abdomen revealed in all patients thickening of the colon wall and pericolic edema, and a pericolic abscess was revealed in three of them. Both clinical and radiologic findings supported the diagnosis of acute neutropenic enterocolitis. All patients were successfully treated with broad-spectrum antibiotics and recombinant human granulocyte colony-stimulating factor. In conclusion, acute neutropenic enterocolitis is a severe complication of taxane-based chemotherapy. Early diagnosis and appropriate conservative treatment leads to complete recovery. Although rare, this infection is less often associated with other chemotherapeutic regimens.

Thalidomide is an active agent in patients with refractory multiple myeloma. Based on these data we performed a phase II study in order to evaluate the activity of thalidomide in Waldenstrom's macroglobulinemia (WM). Thalidomide was administered on a doseescalating schedule of 200 mg daily p.o. x 14 days with dose escalation by 200 mg every two weeks to a maximum dose of 600 mg. Twenty patients were treated with a median age of 74 years (range: 48 to 85 years). Hemoglobin was < 10.0 gr/dl in 5 patients, serum monoclonal IgM was >3.0 gr in 9 patients and lymphadenopathy and splenomegaly were present in 7 and 10 patients respectively. Ten patients were previously untreated, 1 was relapsing off treatment, 5 were primary refractory and 4 were treated during refractory relapse. Five patients (25%) achieved at least 50% reduction of serum monoclonal IgM and at least 50% reduction of tumor at all involved sites. At least 25% reduction of IgM was noted in all eventual responders within 4 weeks of thalidomide treatment. Responses occurred in 3 of 10 previoulsy untreated patients and in 2 of 10 pretreated patients. One responding patient with artial fibrillation died of an embolie cerebral accident 4 months after achieving a response and the other responding patients remain without progression for 2+ months to 12 + months. Some degree of toxicity was observed in almost all patients. Grade 2 or 3 toxicities included constipation in 6 patients, somnolence in 3 patients, tremor in 2 patients and neuropathy in 2 patients. This explained the inability to reach the targeted dose of thalidomide 600 mg p.o. QD in all but 4 patients; the median daily dose of this agent was 200 mg. We conclude that thalidomide has moderate activity in WM. A relatively low median daily dose could be administered to this elderly patient population.