Gentle yet effective treatment for elderly patients with refractory or relapsing multiple myeloma

Fourteen patients, aged 65-85 years, with refractory (11) or relapsing (3) multiple myeloma were treated with a "protracted-sequential" protocol comprising vincristine 1-2 mg or vindesine 3 mg/M(2) (max. 5 mg) IVI over 4 hr on D1, prednisolone 40-50 mg PO D1-14, and melphalan 2-4 mg PO or cyclophosphamide 50-100 mg PO D15-28; cycles were repeated at 4-6 weekly intervals. Treatment was continued for 12 months if the response was optimal or indefinitely if the response was suboptimal. Five patients responded optimally; their survival from the commencement of this protocol ranged from 30 to 120 months. The other nine patients achieved a partial response, their survival ranging from 4+ to 79 months. The treatment is simple, nontoxic, and as convenient as the "classic combination" of melphalan and prednisolone.     

Long-term outcome of patients with relapsed and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue.

OBJECTIVE: To review the long-term outcome of patients with recurrent and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. DESIGN: Cohort study. SETTING: A university hospital. PATIENTS: Forty consecutive patients with recurrent or refractory germ cell tumors treated at Indiana University between September 1986 and June 1989. INTERVENTIONS: Patients were treated with high-dose carboplatin (900 to 2000 mg/m2 body surface area) and etoposide (1200 mg/m2). Three patients also received ifosfamide (10 g/m2). All patients had autologous bone marrow rescue. Of the 40 study patients, 26 received two full courses of therapy. MEASUREMENTS: Patient charts were reviewed to determine the rate and duration of complete and partial remission and the number of long-term, disease-free survivors. The influence of cisplatin-refractory disease and the site of the primary tumor on the incidence of remission and survival were also investigated. RESULTS: Of the 40 study patients, 26 (65%) responded to treatment; 12 (30%) achieved a complete response, and 14 (35%) achieved a partial response. Of the 12 complete responders, 5 relapsed, and 1 died of treatment-related acute leukemia 27.5 months after treatment without evidence of germ cell cancer. Six (15%) of the original 40 patients, of whom 3 were refractory to cisplatin, remained in complete remission after at least 24 months of follow-up. Eight of 40 patients had primary mediastinal germ cell tumors with no complete remissions and a median survival of 2 months (range, 0.5 to 9.0 months). CONCLUSIONS: Treatment with high-dose carboplatin and etoposide in conjunction with autologous bone marrow rescue in patients with relapsed or refractory germ cell tumors is a potentially curative therapeutic option, even for heavily pretreated or cisplatin-refractory patients. Some degree of disease resistance to cisplatin can be overcome with dose escalation of platinum compounds. Patients with multiple recurrences of relapsed or refractory primary mediastinal germ cell tumors were not helped by this approach.     

Phase II trial of carboplatin in patients with advanced germ cell tumors refractory to cisplatin

A phase II trial of carboplatin was conducted in 22 patients with advanced germ cell tumors refractory to cisplatin-based chemotherapy. Twenty of 22 patients were evaluable for toxicity and response. Two partial responses and one minor response were seen. The major toxic effect was myelosuppression. Carboplatin has antitumor activity in patients with advanced germ cell tumors refractory to cisplatin, and phase II and III studies of combination chemotherapy are indicated.     

High-dose chemotherapy with autologous stem cell support in poor-risk germ cell tumors

 High-dose chemotherapy (HDT) and stem cell transplantation is a newer treatment option widely applied in poor-risk germ cell tumor patients. Due to the increasing practical clinical experience and the availability of hematopoietic growth factors, this treatment approach has become a relatively safe procedure. Depending on the drugs used, the most prominent therapy-associated side effects are myelosuppression, infections, mucositis, moderate, mostly reversible neurotoxicity, and renal impairment. Because of their unique pharmacologic characteristics, carboplatin and etoposide have proved to be the most important drugs for HDT. It is not known whether the addition of ifosfamide or cyclophosphamide or other drugs to the combination of carboplatin and etoposide leads to superior results. It is not yet clear if HDT should already be instituted in first-line treatment of poor-risk patients, or later after relapse or incomplete response. Even if precise data on the therapeutic value of HDT are still missing because randomized trials are not yet ready for evaluation, there is good evidence for the effectiveness of HDT. The demonstration of remissions in cisplatin-refractory patients, the inversion of remission durations, and the induction of long-term freedom from disease in multiply relapsed patients who were deemed incurable with conventional-dose procedures argue in favor of HDT. Finally, the delineation of prognostic factors associated with a poor probability of survival after HDT contributes to the selection of patients who are likely to profit from HDT and those who should be spared from dose-intensive treatment. Received: 3 March 1998 / Accepted: 27 March 1998     

Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease

The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.     

VAB-3 combination chemotherapy in primary mediastinal germ cell tumors

Ten patients with primary mediastinal nonseminomatous germ cell tumors were treated with the VAB-3 protocol. All patients with measurable disease showed tumor regression with chemotherapy, but only two had sustained partial response allowing thoracotomy and resection of residual tumor after the second induction. Both patients received additional induction therapy and one also received irradiation; they have been free of disease 41+ and 40+ months from the beginning of chemotherapy. All other patients died from the disease.     

ESHAP方案治疗难治性或复发性恶性淋巴瘤的疗效观察

目的：探讨ESHAP方案对难治性或复发性恶性淋巴瘤(Malignant lymphoma，ML)的疗效。方法：采用ESHAP方案治疗36例难治性或复发性恶性淋巴瘤，其中难治性非霍奇金淋巴瘤(NHL)17例，复发NHL16例，难治性或复发性霍奇金淋巴瘤(HL)3例。结果：12例难治性或复发性ML患者达完全缓解(CR率为33．3％)，10例达部分缓解(PR率为27．8％)；总有效率为61．1％，其中生存最长者43个月，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ESHAP方案对部分难治性或复发性ML患者仍有效，毒副作用可以耐受。可用于治疗对其他化疗方案无效的难治性或复发性ML。     

Sexual functions after high-dose chemotherapy in survivors of germ cell tumors

We investigated the changes in sexual function in male patients with germ cell tumor continuously disease free after one or two courses of high-dose chemotherapy with hematopoietic stem cell support. A questionnaire was mailed to 35 patients, and 30 patients sent it back. Sexuality was considered a problem by 10 patients (33%), but no patients considered sexuality a major problem. Erection was more difficult to achieve in seven patients (23%) and 10 patients (33%) experienced increased difficulty in maintaining an erection. Eight patients (27%) had the experience of less intensive and less frequent orgasm. In all, 13 patients (43%) thought that both the disease and treatment had worsened their sexual capacity, but 20 patients (67%) were satisfied with their sex life. Most of the patients (63%) considered that insufficient information and counselling had been given by their physicians about the sexual sequelae of therapy. However, the amount of information about the disease and treatment was considered good by 77 and 80% of the patients, respectively. This study shows that 27% of patients were not content with their ability to attain sexual satisfaction due to the illness or its treatment. Communication is an important issue and better information tools could lead to improved compliance in these patients.     

Lenalidomide in patients with cisplatin-refractory and multiply relapsed germ cell tumors

Objective

Treatment options are still limited in patients with cisplatin-refractory and multiply relapsed germ cell tumors. We evaluated the efficacy and tolerability of lenalidomide within a compassionate use concept.

Patients and methods

Four patients multiply relapsed after platin-based chemotherapies without any further standard treatment option received 25 mg lenalidomide orally on days 1–21 of a 28-day cycle.

Results

All four patients were pretreated with a median number of seven lines of previous chemotherapy (range 4–8), all including platin-based high-dose chemotherapy. After 4 weeks of lenalidomide treatment all patients had progressive disease with increase in serum tumor markers and progression in computed tomography. Median survival time was 8 weeks (range 5–17). The toxicity profile was favorable. No severe toxicities related to lenalidomide occurred in these patients.

Conclusion

Lenalidomide was well tolerated and showed efficacy in heavily pretreated patients with cisplatin-refractory and multiply relapsed germ cell tumors.     

High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors.

We report seven patients with germ cell tumors which either recurred following a minimum of two regimens of platinum-based chemotherapy or were refractory to cisplatin. The patients were treated with one or two courses of high dose carboplatin (CBDCA) and etoposide (VP-16) plus ifosfamide (IFX) with mesna uroprotection and autologous bone marrow support. The doses given were CBDCA 500 mg/m2 every other day x 3 and VP-16 400 mg/m2 every other day x 3. IFX was given in a dose of 2 g/m2 daily x 5 days with mesna. The original intent of the protocol was to explore escalating doses of IFX, but excessive renal toxicity at the first dose level prevented escalation. Of the seven patients treated, four developed a marked decline in their renal function and three of the four required hemodialysis or hemofiltration. Six of seven patients treated had a decline in their serum markers indicating a response to therapy, but all have relapsed. Our conclusion is that while the combination of CBDCA/VP-16/IFX with ABMT is active in this group of patients, it is associated with excessive renal toxicity which is probably due to underlying renal dysfunction secondary to extensive prior cisplatin-based chemotherapy.     

Transient tumor marker elevation following chemotherapy for germ cell tumors of the testis

A total of 22 adults with metastatic nonseminomatous germ cell tumor of the testis and raised pretreatment serum levels of the beta subunit of human chorionic gonadotropin (HCG) had serial monitoring of serum HCG by weekly assay following initiation of chemotherapy with bleomycin, etoposide, and cisplatin (BEP). A transient rise in HCG (the marker "surge") was detected in 9 patients (41%), of whom one relapsed. None of the other 13 patients have relapsed (follow-up, 24-60 months), and the BEP regimen overall leads to an 83.3% disease-free survival (Br J Cancer 47:613-619, 1983). The marker surge is not an adverse prognostic factor during initial chemotherapy.