Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol

From January 1993 to March 1995, 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol. 133 patients had localised disease, while 29 had metastases at diagnosis. These last patients were simultaneously operated upon for their primary and metastatic lesions. Chemotherapy consisted preoperatively of two cycles of high dose methotrexate (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned drugs used as single agents. The mean follow-up of all patients was 6.5 years (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event-free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients with localised disease, and 17 and 24% for patients with metastases at diagnosis. These results did not differ from those achieved in our previous study (IOR/OS-3) in which IFO was used only postoperatively in poor responders.     

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

PURPOSE: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. PATIENTS AND METHODS: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. RESULTS: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. CONCLUSION: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01).     

Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: Analogies and differences between the two tumors

Background: Malignant fibrous histiocytoma (MFH) is a rare bone tumor usually treated like osteosarcoma. Studies on analogies and differences between the two tumors have seldom been reported.Patients and methods: Between March 1982 and December 1994, 51 patients with high-grade MFH of bone and 390 with high-grade osteosarcoma were treated with the same regimen of neoadjuvant chemotherapy. All of the tumors in both groups were located in the limbs. Preoperative chemotherapy was performed according to three different, successively activated, regimens consisting of MTX/CDP intraarterially, MTX/CDP/ADM, and MTX/CDP/ADM//IFO.Results: The rate of limb salvage was the same in both the MFH (92%) and osteosarcoma (85%) patients. MFH showed a statistically significantly lower rate of good histologic response, 90% or more tumor necrosis (27% vs. 67%, P = 0.00001) for all three regimens. Despite this low chemosensitivity, the disease-free survivals of the two neoplasms were similar (67% vs. 65%).Conclusions: In terms of histologic response to primary chemotherapy, MFH has a lower chemosensitivity than osteosarcoma. Nevertheless, the two tumors have similar prognoses when treated with chemotherapy regimens based on MTX, CDP, ADM and IFO.     

Comparative Outcome of Thai Pediatric Osteosarcoma Treated with Two Protocols: the Role of High-Dose Methotrexate (HDMTX) in a Single Institute Experience

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy againstpediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA),doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility andeffectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO[MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods:A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with twochemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+)protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatmentregimens were 43.4±6.0% and 53.2±6.1% respectively. The 3-year DFS and OS were improved significantlywith the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [69.8±10.5%,79.8±9.1% for MTX(+) and 31.1±6.9%, 42.2±7.4% for MTX(-) protocol, respectively]. Patients with metastaticosteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS thanthose treated with the MTX(-) protocol (66.7±13.6% and 15.0±8.0% for 3-year DFS, p=0.010, 73.3±13.2% and20±8.9% for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFSand OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. Themultivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor ofinferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Ourstudy demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survivalrate in pediatric osteosarcoma cases, in line with reports from developed countries.     

Influence of Adriamycin Dose in the Outcome of Patients with Osteosarcoma Treated with Multidrug Neoadjuvant Chemotherapy: Results of Two Sequential Studies

Summary

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m² instead of 360 mg/m²) or the single dose per cycle of this drug (60 mg/m² instead of 90 mg/m²) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol – in comparison with the first protocol – after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51 – 73% vs 123/144 – 85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.     

Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol

The results of the Rizzoli IOR/OS-3b neoadjuvant protocol for the treatment of osteosarcoma of the extremity are reported. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX i.v.), followed by a combination of cisplatin (CDP i.a.)/ doxorubicin (ADM i.v.). Postoperatively all patients, regardless of the histologic response, received 3 more cycles of MTX, CDP/ADM alternated with 3 cycles of ifosfamide. In the study performed between January and December 1992 43 patients were enrolled and limb salvage was performed in 39 of them (91%). The histologic response to chemotherapy was good (90% or more tumor necrosis) in 24 patients (56%) and poor (less than 90% tumor necrosis) in 19 (44%). With a minimum follow-up of 7 years, 23 pts (53%) remained continuously free of disease, 19 relapsed and one died due to unrelated cause. In spite of the high number of limb salvages performed, only 2 local recurrences were registered. The 7-year event-free survival and overall survival were, respectively, 53% and 68%. The hematopoietic and extrahematopoietic toxicity experienced by the patients during the entire treatment was relatively mild. These long-term results confirm that, with neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with osteosarcoma of the extremities, avoiding amputation in most of them. These results, however, are no better than those achieved in our previous study IOR/OS-3a, in which only poor responder patients received ifosfamide during the postoperative treatment.     

The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively

The relationship between dose-intensity and outcome was retrospectively analyzed in 125 patients with osteosarcoma of the extremities treated at our institution with neoadjuvant chemotherapy between 1986 and 1988. Before surgery, chemotherapy was performed with high-dose methotrexate (HDMTX) i.v. followed by cisplatinum (CDP) i.a. and adriamycin (ADM) i.v. Postoperative chemotherapy was tailored according to the necrosis induced by preoperative treatment. Patients who were "good responders" had 31-weeks of chemotherapy with the same drugs utilized preoperatively, while "poor responder" patients received a longer treatment (40 weeks) in which ifosfamide and etoposide (VP-16) were added to HDMTX, CDP and ADM. At a median follow-up of 2 years (1-3 years) 100 patients (80%) remained continuously disease-free and 25 patients relapsed: 24 with lung metastases and 1 with local recurrence. According to the real dose-intensity received, calculated as a percentage of the dose intensity projected by the protocol, the continuously disease-free survival was 87% in the 82 patients who received 80% or more of the scheduled dose-intensity and only 65% for the 43 patients who received less than 80% of the projected dose-intensity. This difference is highly significant (P less than 0.01). These results suggest that in neoadjuvant chemotherapy of osteosarcoma the real dose-intensity delivered is a determinant of treatment outcome and therefore every effort should be made to avoid reductions of doses and delays of cycles of chemotherapy in these patients.     

The Importance of Dose-Intensity in Neoadjuvant Chemotherapy of Osteosarcoma: A retrospective analysis of high-dose methotrexate,cisplatinum and adriamycin used preoperatively

Summary

The relationship between dose-intensity and outcome was retrospectively analyzed in 125 patients with osteosarcoma of the extremities treated at our institution with neoadjuvant chemotherapy between 1986 and 1988. Before surgery, chemotherapy was performed with high-dose methotrexate (HDMTX) i.v. followed by cisplatinum (CDP) i.a. and adriamycin (ADM) i.v. Postoperative chemotherapy was tailored according to the necrosis induced by preoperative treatment. Patients who were «good responders» had 31-weeks of chemotherapy with the same drugs utilized preoperatively, while «poor responder» patients received a longer treatment (40 weeks) in which ifosfamide and etoposide (VP-16) were added to HDMTX, CDP and ADM. At a median follow-up of 2 years (1-3 years) 100 patients (80%) remained continuously disease-free and 25 patients relapsed: 24 with lung metastases and 1 with local recurrence. According to the real dose-intensity received, calculated as a percentage of the dose intensity projected by the protocol, the continuously disease-free survival was 87% in the 82 patients who received 80% or more of the scheduled dose-intensity and only 65% for the 43 patients who received less than 80% of the projected dose-intensity. This difference is highly significant (P < 0.01).

These results suggest that in neoadjuvant chemotherapy of osteosarcoma the real dose-intensity delivered is a determinant of treatment outcome and therefore every effort should be made to avoid reductions of doses and delays of cycles of chemotherapy in these patients.     

A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.

AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.) infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported. METHODS: Two successive randomized studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM) within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO, within a four-drug regimen was tested. RESULTS: The rate of responses to chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen (76%vs 62%). According to the route of CDP infusion, in the three-drug regimen the rate of responses was significantly higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated i.v. (46%); with the four-drug regimen the rate of response was not significantly different in patients treated i.a. (81%) and in patients treated i.v. (71%). No significant differences in the rates of limb salvages, local recurrence and event-free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION: In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does not offer any significant advantage when this drug is used within an aggressive, multiagent, pre-operative four-drug regimen. Copyright Harcourt Publishers Limited.     

Neoadjuvant Chemotherapy for High Grade Osteosarcoma of the Extremities: Long-Term Results for Patients Treated According to the Rizzoli IOR/OS-3b Protocol

Abstract

The results of the Rizzoli IOR/OS-3b neoadjuvant protocol for the treatment of osteosarcoma of the extremity are reported. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX i.v.), followed by a combination of cisplatin (CDP i.a.)/ doxorubicin (ADM i.v.). Postoperatively all patients, regardless of the histologic response, received 3 more cycles of MTX, CDP/ADM alternated with 3 cycles of ifosfamide. In the study performed between January and December 1992 43 patients were enrolled and limb salvage was performed in 39 of them (91%). The histologic response to chemotherapy was good (90% or more tumor necrosis) in 24 patients (56%) and poor (less than 90% tumor necrosis) in 19 (44%). With a minimum follow-up of 7 years, 23 pts (53%) remained continuously free of disease, 19 relapsed and one died due to unrelated cause. In spite of the high number of limb salvages performed, only 2 local recurrences were registered. The 7-year event-free survival and overall survival were, respectively, 53% and 68%. The hematopoietic and extrahematopoietic toxicity experienced by the patients during the entire treatment was relatively mild.

These long-term results confirm that, with neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with osteosarcoma of the extremities, avoiding amputation in most of them. These results, however, are no better than those achieved in our previous study IOR/OS-3a, in which only poor responder patients received ifosfamide during the postoperative treatment.     

洛铂联合阿霉素、异环磷酰胺化疗方案新辅助治疗骨肉瘤的剂量探索

目的 探讨洛铂（LBP）联合阿霉素（ADM）、异环磷酰胺（IFO）化疗方案新辅助治疗骨肉瘤的最大耐受量（MTD）,并观察其毒副反应。方法 LBP设定3个剂量水平,分别为45mg／m²、50mg／m²、55mg／m²,ADM和IFO剂量固定（ADM 60mg／m²、IFO 12g／m²）,观察到出现剂量限制性毒性（DLT）即终止试验,或至55mg／m²未出现DLT,试验亦终止。结果 共有6例患者完成了爬坡试验,当试验进行到第1个剂量组时,出现2例DLT,试验终止。从而确定联合化疗方案的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO 12g／m²。主要不良反应为骨髓抑制,血小板减少的发生率为66.6％（4/6）,3级发生率为33.3％（2/6）;白细胞减少的发生率为83.3％（5/6）,未发生4级白细胞减少;中性粒细胞减少的发生率为83.3％（5/6）,4级发生率为33.3％（2/6）。所有患者经对症治疗后均好转,未影响继续治疗。结论 LBP联合ADM、IFO化疗方案新辅助治疗骨肉瘤的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO12g／m²,毒副反应可耐受,建议以此为依据开展进一步临床研究。     

Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities. The Istituto Rizzoli Experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin

Between March 1983 and June 1986 127 patients with localized osteosarcoma of the extremity were treated with neoadjuvant chemotherapy. Preoperative chemotherapy consisted of two cycles of methotrexate (MTX) (high or moderate doses) followed by 6 days by cisplatin (CDP). Surgery was an amputation or a rotation plasty, or a limb salvage. Necrosis was good in 52% of cases, fair in 36%, and poor in 12%. Postoperative chemotherapy consisted of Adriamycin (doxorubicin [ADM]) and bleomycin (BCD) for poor responders; and ADM, MTX, and CDP for fair responders. Good responders were treated as fair responders or with only MTX and CDP. At a 47-month follow-up, 66 patients remained continuously disease free and 61 patients developed metastases. Six of these patients had also a local recurrence. According to the grade of necrosis, the cumulative disease-free probability at 5 years was 67% for good responders, 42% for fair responders, and for poor responders 10% at 45 months. According to the doses of MTX, survival at 5 years was 58% for patients who received high doses and 42% for patients treated with moderate doses. No differences in the rate of survivors were observed between amputated patients and patients treated with limb salvage. The authors conclude that (1) a limb salvage procedure is possible in about 70% of cases and as safe as demolitive surgery, if adequate surgical margins are achieved; (2) good responders have a better prognosis than fair and poor responders if postoperative chemotherapy is sufficiently prolonged and also includes ADM; (3) a different postoperative chemotherapy for poor responders did not improve their prognosis; and (4) a multidrug regimen using high doses of MTX is probably more effective than moderate doses.     

Phase I study of twelve-day prolonged infusion of high-dose ifosfamide and doxorubicin as first-line chemotherapy in adult patients with advanced soft tissue sarcomas.

PURPOSE: To determine whether a prolonged 12-day continuous infusion allows the administration of high-dose ifosfamide (IFO) with an acceptable toxicity profile when combined with full-dose doxorubicin (Adriamycin; ADM) as first-line chemotherapy in patients with advanced soft tissue sarcomas. PATIENTS AND METHODS: Escalating doses of continuous infusion IFO (8-15 g/m2) given on days 1 to 12 in combination with ADM 75 mg/m2 given on day 8 and prophylactic granulocyte colony-stimulating factor support were administered every 4 weeks to 35 chemona?ve patients with advanced soft tissue sarcomas. RESULTS: The maximum tolerated dose was IFO 15 g/m2. Hematological toxicity was the main dose-limiting toxicity and was dose dependent. Furthermore, thrombocytopenia was cumulative. Grade 4 (WHO) neutropenia and thrombocytopenia were recorded in 48% and 14% of courses, respectively. Eight patients experienced febrile neutropenia. A partial response was observed in 16 out of 30 assessable patients [53%, 95% confidence interval (CI) 25-63]; median time to progression was 25 weeks (range 4-91). CONCLUSIONS: This study proved that a prolonged 12-day continuous infusion allows an increase in the total IFO dose that can be safely combined with ADM. A multicentric phase II study by the Italian Sarcoma Group to assess its antitumor activity is currently ongoing in patients with advanced soft tissue sarcomas.     

甲氨蝶呤、顺铂、阿霉素和异环磷酰胺治疗ⅡB期肢体骨肉瘤的临床观察

目的 观察大剂量甲氨蝶呤（MTX）、顺铂（DDP）、阿霉素（ADM）和异环磷酰胺（IFO）4种药物两种不同组合方案治疗ⅡB期肢体骨肉瘤的疗效及毒副反应。方法 回顾性分析接受4种药物化疗方案的185例ⅡB期肢体骨肉瘤患者,其中93例接受意大利IOR-OS／N-5方案（MTX 8～12g／m²静滴6h,d₁;用药后12h亚叶酸钙解救12次,每次15mg;DDP 80～100mg／m²、ADM 60mg／m²静滴,d8;IFO 2.0g／m²静滴,d₂₁～d₂₅;美司那400mg每天IFO用后第0、4、8h静滴）,92例接受优化方案（除ADM由第8天静滴改为第21天与IFO联用外,其他同IOR-OS／N-5方案）。比较两种方案的疗效及毒副反应。结果 IOR-OS／N-5方案和优化方案组的保肢率分别为52.7％（49／93）和58.7％（54／92）。两组患者的3年复发率分别为14.0％、7.6％,3年转移率分别为47.3％、30.4％,差异均有统计学意义（P＜0.05）;两组患者的3年生存率分别为57.0％、75.0％,差异有统计学意义（P＜0.05）。两组患者的中位无病生存时间（DFS）分别为22.2个月（95％CI：16.2～28.2个月）和29.0个月（95％CI：23.8～34.3个月）,差异有统计学意义（P=0.024）;两组患者的中位总生存时间（OS）分别为32.2个月（95％CI：23.2～38.2个月）和36.1个月（95％CI：33.8～44.3个月）,差异有统计学意义（P=0.032）。两组患者的主要毒副反应为肝功能损害、骨髓抑制、恶心呕吐等。其中3、4级肝功能损害的发生率分别为35.2％、16.6％,3、4级白细胞减少的发生率分别为22.6％、30.2％。结论 将大剂量MTX、DDP、ADM和IFO这4种药物进行优化组合治疗骨肉瘤患者的耐受性好,疗效提高。     

异环磷酰胺联合长春瑞滨治疗对铂类耐药的复发和／或转移性鼻咽癌

 目的 探讨异环磷酰胺（IFO）联合长春瑞滨（VRL）治疗对铂类耐药的复发和／或转移的鼻咽癌的疗效和毒副反应。方法 VRL 25 mg／m2，静脉推注，第1，5天；IFO 1 200 mg／m2，静脉滴注3 h，第1 ~ 5天；美斯纳400 mg，静脉推注，IFO开始后0，3，6 h。21 d为1疗程，至少完成2周期作疗效评价。结果 25例患者中，完全缓解（CR）2例，部分缓解（PR）12例，总有效率（CR+PR）为56.0 %，稳定8例，临床获益率（CBR）为88.0 %；疾病进展3例；中位疾病进展时间（TTP）为7.1个月（范围2.0～21.0个月），1年生存率为55 %。主要毒副反应为骨髓抑制和静脉炎。结论 IFO联合VRL治疗对铂类耐药的复发和／或转移的鼻咽癌疗效可靠，毒副反应可耐受。     

利妥昔单抗联合高剂量治疗和自体外周血干细胞移植治疗侵袭性B细胞淋巴瘤的多中心前瞻性研究

目的 探讨在高剂量治疗联合自体外周血干细胞移植的基础上,加用利妥昔单抗治疗侵袭性B细胞淋巴瘤的可行性和疗效.方法 12个癌症研究中心共入组28例侵袭性B细胞淋巴瘤患者,其中22例为新诊断患者,6例为复发患者.每例患者共接受4次利妥昔单抗静脉输注,即在外周血干细胞动员化疗的前1天、动员化疗的第7天、干细胞回输的前1天和回输后的第8天各给予1次,每次375 mg/m2,共1500 mg/m2结果 高剂量治疗后,所有患者均达到完全缓解.中位随访37个月时,全组患者的4年总生存率和无进展生存率分别为75.0%和70.3%,新诊断患者的4年总生存率和无进展生存率均为72.7%.全组患者对利妥昔单抗治疗的耐受性较好,不良反应多为1、2度.结论 在高剂量治疗联合自体造血干细胞移植的基础上加入利妥昔单抗治疗侵袭性B细胞淋巴瘤是可行的,并且可能使患者的生存获益.     

Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response

Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival (MFS) in osteosarcoma, a randomized study was undertaken with the aim of (1) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin (DOX) and cisplatin (CPDD) by administering these drugs postoperatively only after poor response with a milder preoperative regimen, and (2) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively. The available patients were divided into two groups. Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate (HDMTX) and the triple drug combination of bleomycin, cyclophosphamide, and dactinomycin (BCD) and were switched to DOX/CPDD postoperatively in case of poor response. DOX/CPDD was used besides HDMTX for initial treatment in the control arm, and BCD alternatively with CPDD/ifosfamide (IFO) for postoperative salvage treatment. The response rate of the study arm was significantly inferior to the control arm (26% v 60%; P less than .001). The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm (41%); it was unchanged in the control arm (53%) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy (52%). The actuarial 4-year MFS rate of good responders was 73% in the study arm, 79% in the control arm, and not significantly different from that of the COSS-80 study (84%), although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study. The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm (49% v 68%; P less than .1) and also inferior to the COSS-80 study (68%; P less than .01), indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment.     

High-dose ifosfamide plus adriamycin in the treatment of adult advanced soft tissue sarcomas: Is it feasible?

Background: Adriamycin (ADM) and ifosfamide (IFO) are the two most active agents in the treatment of soft tissue sarcomas (STS) with a clear dose-response relationship. We evaluated the feasibility and toxicity of a high-dose IFO-plus-ADM combination.Patients and methods: Fourteen patients with advanced disease and nine patients in adjuvant setting received IFO 12.5 g/m² in 120-hour continuous infusion with Mesna uroprotection and ADM 20 mg/m² on days 1–3 and G-CSF every three weeks.Results: Twenty-three patients received 89 chemotherapy cycles (70 cycles at full dose). Seventeen patients received the planned treatment, and nine patients required dose reductions. We observed grade 3–4 neutropenia in 52 cycles (59%)/20 patients; grade 3–4 thrombocytopenia in 16 cycles (18%)/nine patients; grade 3–4 anaemia in 24 cycles (27%)/11 patients. Eight patients experienced febrile neutropenia and six patients required blood transfusions.Conclusions: While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation.     

Combination chemotherapy of diffuse large-cell non-Hodgkin's lymphoma--superiority of the adriamycin combination

In patients with diffuse large-cell non-Hodgkin's lymphoma, the results of combination chemotherapy containing adriamycin (ADM) were compared with those of combination chemotherapy without ADM. None of the patients had had any prior therapy and there was no difference in any other background factors for these two treatment groups. Of 32 patients treated without ADM, 19 (59%) achieved complete response (CR) and 12 (38%) achieved partial response (PR). Of 20 patients treated with ADM. 14 (70%) achieved CR and 6 (30%) achieved PR. For patients treated without ADM, median duration of CR was 9 months, projected 5-year relapse-free rate was 27%, median survival time was 1 year 6 months and projected 5-year survival rate was 27%. For patients treated with ADM, median duration of CR was not reached, projected 5-year relapse-free rate was 85%, median survival time was 2 years 2 months and projected 5-year survival rate was 49%. Combination of ADM was superior and therefore should be used for the initial treatment of this type of non-Hodgkin's lymphoma.     

以异环磷酰胺、顺铂、长春地辛联合化疗为主综合治疗小细胞肺癌的疗效观察

目的　观察异环磷酰胺 (IFO)、顺铂 (DDP)、长春地辛 (VDS)联合化疗为主综合治疗小细胞肺癌的疗效及毒副反应。方法　 3 6例小细胞肺癌采用IFO 2 .0静滴连用 5天 ,MESNA 40 0mg于IFO后 0、4、8h静脉输注 ,VDS 5mg第 1、8两天静脉输注 ,DDP 40mg静脉滴注 ,连用 3天。 2 1天为一周期 ,2～ 4周期后给予放疗。之后再按原方案化疗 4～ 6周期止并评价疗效。结果　总有效率为 72 .2 %( 2 6/3 6) ,其中初治者 84.0 % ( 2 1/2 5 ) ,复治者 45 .5 % ( 5 /11) ;1年生存率为 75 .0 % ,3年生存率为 3 6.1%。主要毒副反应为骨髓抑制。结论　以异环磷酰胺、顺铂、长春地辛联合化疗为主的综合治疗小细胞肺癌能有效地提高患者近期和远期疗效 ,毒副反应能够耐受。