Cisplatin and vindesine for disseminated non-small cell lung cancer. Results of a prospective trial with 81 patients

Eighty-one patients with disseminated non-small cell lung cancer (stage IV) were treated with 2 monthly cycles of initial chemotherapy combining cisplatin with vindesine. The initial chemotherapy-responding patients (CR, PR, MR) were randomized to 2 cycles or 4 cycles of maintenance chemotherapy. After initial chemotherapy, the response rate was 33% (CR, PR, MR) with 18.5% objective responses. The overall 1-year survival rate was 15% with 37% for responders as opposed to 2% for non-responders. Maintenance chemotherapy did not improve the response rate obtained after initial cycles. The small number of patients does not allow us to reach a definite conclusion on the optimum duration of maintenance chemotherapy. In the absence of large placebo versus chemotherapy randomized trials, no definite conclusion can be made on the benefit of chemotherapy in disseminated non-small cell lung cancer. This study suggests, however, that chemotherapy is associated with a significantly longer survival in responding patients.     

Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas

PURPOSE: To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50-99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. METHODS AND MATERIALS: From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50-75%) response (n = 25), or unconfirmed complete (76-99%) response (n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy (n = 32) or chemotherapy (n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR). RESULTS: Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated. CONCLUSION: Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.     

Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.     

Effect of Neoadjuvant Chemotherapy on Improvement of Surgical Resectibility and Survival of Patients with Stage ⅢA Non Small Cell Lung Cancer

Objective To assess the effect of neoadjuvant chemotherapy on surgical resectibility and surival in patients with stage III A non small cell lung cancer (NSCLC). Methods 42 patients with stage III A NSCLC were randomized to receive either two cycles chemotherapy followed by surgery (neoadjuvant chemotherapy group) or surgery alone (surgery alone group). All patients received four cycles chemotherapy after surgery. Results The overall response to chemotherapy was 42.9% (38.1% partial response and 4.8% complete response). Toxicity of chemotherapy was minor and consisted mainly of gastroenterological side effects and myelosuppression. Patients treated with neoadjuvant chemotherapy had estimated surgical resection rate of 95.2% (n=20) and a complete resection rate in 52.4% (n=11) compared to 66.7% (n=14) and 28.6% (n=6) respectively, for patients with surgery alone (P<0.05). None of the patients died from the operation. The median survival was 24.6 months in the neoadjuvant chemotherapy group as compared to only 10.8 months in the surgery alone group (P<0.05). The 2-year survival rate was 57.1% in the chemotherapy group as compared to 28.6% in the surgery alone group (P<0.05). Conclusion Neoadjuvant chemotherapy improves the surgical resectibility and increases the median survival and 2-year survival rate of patients with stage III A NSCLC. This study was supported by the Jiangsu Provincial Scientific and Technology Committee (BS200376).     

Results of cisplatin-based polychemotherapy and analysis of prognostic factors in ovarian cancer. Apropos of 106 cases

One hundred and six patients with stage Ic to IV ovarian carcinoma were treated by a protocol consisting of optimal debulking surgery followed by 9 cycles of CHAP chemotherapy. Clinical response was confirmed by a second-look procedure. Sixty-nine patients (65%) responded with 54 histological complete remissions (50.8%). Nineteen patients did not receive any complementary treatment due to a negative reaction, or prolonged neutropenia. Seven patients received maintenance chemotherapy, 10 an abdominal radiotherapy, 22 intraperitoneal chemotherapy and 11 autologous bone marrow transplantation. The 5-year survival rate was 32.5% and disease-free survival rate was 39.7%. Prognostic-factor analysis showed that age, initial staging, residual disease and cytological grading were significant. The authors propose a classification based on the risk of relapse, and different therapeutic indications for improving response rate and patient survival.     

Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy.

PURPOSE: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. PATIENTS AND METHODS: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)-based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. RESULTS: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). CONCLUSION: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.     

Combined antiestrogen and cytotoxic therapy with pseudomonas vaccine immunotherapy for metastatic breast cancer. A prospective, randomized trial

One hundred thirty-three consecutive, previously untreated patients who had metastatic breast cancer were treated with a combination of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). They were randomly assigned to receive nonspecific immunotherapy with a heptavalent pseudomonas vaccine. Sixty-five patients were treated with pseudomonas vaccine, whereas 68 did not receive immunotherapy. In addition, all patients with estrogen receptor-positive tumors or tumors with an estrogen receptor status were also treated with tamoxifen. To allow clinical assessment of hormone sensitivity in vivo, tamoxifen was started 6 weeks before chemotherapy except in patients who had life-threatening disease. After the initial 6 weeks of tamoxifen, 3% of patients had achieved a complete remission, 9% a partial remission, while 16% achieved a minor response. The maximum response after tamoxifen and chemotherapy included complete remissions in 20% of patients and partial remissions in 61% of patients for an overall remission rate of 81%. The median response duration was 15 months, and the median survival time, 27 months. There were no differences in remission rate, remission duration, or survival time between the groups treated with or without pseudomonas vaccine. Eleven patients with limited metastatic disease received radiotherapy consolidation to initially involved sites. In these patients the median time from radiotherapy to progression of disease was 33 months, and the median survival time was 46 months. We conclude that nonspecific immunotherapy with pseudomonas vaccine failed to increase remission rate or survival time. Furthermore, the addition of tamoxifen to FAC chemotherapy did not improve the remission rate or duration compared to a recent, historical control group of patients treated with only FAC chemotherapy.     

Hyper-CVAD方案治疗淋巴母细胞淋巴瘤

 目的　观察Hyper-CVAD方案对淋巴母细胞淋巴瘤（LBL）的疗效及其毒副作用。方法　2003年11月至2006年12月收治LBL患者40例,其中20例接受Hyper-CVAD／MA方案交替治疗8个疗程;另20例予常规急性淋巴细胞白血病方案,包括VDCLP、CAT、HD-MTX、EA等方案交替治疗,后予维持治疗。结果　Hyper-CVAD方案组：诱导化疗结束后CR18例（90 ％）,PR2例（10 ％）,总有效率100 ％,3年无病生存率（DFS）55 ％,总体生存率（OS）66 ％。常规急淋方案组：诱导化疗结束后CR17例（85 ％）PR1例（5 ％）,PD2例（10 ％）,总有效率90 ％,3年DFS 35 ％,OS 52 ％。两组患者在诱导期的CR率和有效率差异无统计学意义。3年DFS和3年OS的差异均有统计学意义（P＜0.05）。结论　Hyper-CVAD方案可以提高LBL患者的长期无病生存率,可作为LBL一线治疗方案之一。     

小细胞肺癌的三维适形放射治疗

目的 分析三维适形放射治疗（3DCRT）在小细胞肺癌（SCLC）治疗中的可行性、效果和放射损伤情况。方法 19例SCLC患者中,局限期18例,广泛期1例。18例采用放化疗综合治疗,1例采用单独放疗。放疗单次剂量2Gy,每周5次,中位总剂量54Gy。化疗多采用卡铂或顺铂＋VP-16为主的方案,4～6个周期。中位随访24个月。结果 （1）全组患者CR率为31．6％（6／19）,PR率为47．4％（9／19）,SD率为21．1％（4／19）,有效率为79．0％。1年总生存率（OS）为71、7％,2年OS为35．8％,中位生存时间为19个月。1,2年无局部进展生存率均为94．7％。（2）2级急性放射性肺损伤为5．3％（1／19）,2级晚期放射性肺损伤为5．3％（1／19）,2级急性放射性食管损伤10．5％（2／19）,2级血液学毒性为10．5％（2／19）。结论 3DCRT用于SCLC治疗是可行的,患者能够获得较好的近期疗效和2年生存率,SCLC的三维适形放射治疗值得进一步研究。     

不可切除Ⅲ A(N2)期非小细胞肺癌的术前化疗

目的探讨不能切除的ⅢA（N2）期非小细胞肺癌（NSCLC）的治疗方法。方法1999年1月至2002年12月,76例不可切除ⅢA（N2）期NSCLC患者接受诺维苯（NVB,25mg／m^23,第1,5天）加卡铂（300mg／m^2,第1天）2个周期的化疗,第二周期化疗后3周重新评估能否手术切除。对化疗效果达到部分有效（PR）或完全有效（CR）、估计能完全切除的64例患者行剖胸探查术;对化疗后评价为稳定（SD）和进展（PD）的12例患者行放疗。64例手术患者中,完全切除（肺叶或全肺切除加纵隔淋巴结清扫术,至少达到R3水平）56例,术后继续给予诺维苯加卡铂化疗2个周期;不完全切除8例,另加局部放疗。结果76例不可切除的ⅢA（N2）期NSCLC经诱导化疗后手术或放疗,中位生存期为18．6个月,1,2,3年生存率分别为64．2％、39．4％和25．6％。其中完全切除患者的中位生存期为28．2个月,1,2,3年生存率分别为70．4％、52．5％和38．6％。结论对不可切除的局部晚期NSCLC,如诱导化疗后可以手术,应首选外科治疗。     

Multimodal treatment for inflammatory breast cancer

This is a retrospective study of 61 patients with clinically diagnosed breast cancer (IBC) treated with multimodality therapy between September 1977 and September 1985. All patients were scheduled to receive three courses of doxorubicin-based chemotherapy followed by mastectomy, further chemotherapy, and postoperative irradiation. Ten patients (16%) obtained a complete response, defined as either resolution of the clinical signs of inflammatory breast cancer (IBC) (4 patients) or no evidence of tumor in the mastectomy specimen (6 patients). Twenty-seven patients (45%) obtained a partial response, defined as a greater than 50% reduction in the clinical signs of inflammatory breast cancer. No response occurred in 24 patients (39%). Immediate mastectomy was done in 56 patients. Five patients whose disease was not resectable received preoperative irradiation. Nine patients at high risk for locoregional failure received postoperative irradiation immediately after mastectomy and before additional chemotherapy. Postoperative irradiation was given to the chest wall and peripheral lymphatics using standard or accelerated fractionation to a maximum dose of 60 Gy. Forty-six patients completed planned treatment including chemotherapy, surgery, and radiotherapy without failure. The minimum follow-up was 36 months. The 5-year actuarial disease-free survival was 70% for the complete response group, and 35% for the partial response group. All patients with no response failed by 34 months. The actuarial 5-year disease-free survival rate for the entire group was 27%. The 5-year actuarial locoregional control was 89% in the complete response group, 68% in the partial response group, 33% in the no response group, and 58% for all patients. Most failures were on the chest wall within the irradiated volume. Chest wall failures were more frequent in those who did not achieve brisk erythema or moist desquamation after postoperative irradiation. We conclude that multimodal treatment of patients with inflammatory breast cancer results in a low incidence of failure if complete response is obtained following initial chemotherapy. The locoregional control rate and actuarial 5-year disease-free survival for the entire group were not improved when mastectomy was done. Surgery should be done in those patients who respond adequately to chemotherapy, so that late sequelae of high-dose breast irradiation can be eliminated. Higher doses of postoperative irradiation may be required to improve local control in those patients with the poorest response to initial chemotherapy.     

Invasive bladder cancer: a single-institution experience with bladder-sparing approach

Our objective was to assess the efficacy and safety of a selective bladder-preserving approach by transurethral resection and sequential chemoradiotherapy in patients with muscle-invasive bladder cancer. From 1989 through 1997, 40 patients with biopsy-confirmed bladder cancer, clinical stages T2-4NxM0, were treated with induction by aggressive transurethral resection (TUR) and three cycles of methotrexate, cisplatin, and vinblastine (MCV) chemotherapy. Tumor response was evaluated by cystoscopy and biopsy. In complete responders, the treatment was continued by radiotherapy (60 Gy to the bladder and 50 Gy to pelvic lymph nodes). Radical cystectomy was recommended to patients with residual tumor. Clinical complete response rate to TUR and MCV chemotherapy was 70%. The 4-year actuarial overall survival rate for the whole series was 80.5%. Among 36 patients who completed chemotherapy and radiotherapy, the 4-year actuarial survival was 84%, with 82.6% surviving with their bladders intact. Freedom from local failure in complete responders to TUR-chemotherapy was 84%. Multivariate analysis revealed that the extent of initial TUR and status after TUR-chemotherapy were independent prognostic factors associated with survival and disease-free survival. This study confirms that the combination of aggressive TUR and sequential chemoradiotherapy with bladder preservation is an alternative treatment option to primary cystectomy for selected patients with invasive bladder carcinoma.     

Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in China

Aim:   The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC).
Methods:   Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery.
Results:   The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm ( P  = 0.04 and P  = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm.
Conclusion:   Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.     

Extensive disease small cell carcinoma of the lung: trial of non-cross resistant chemotherapy and consolidation radiotherapy

Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.     

早期鼻腔NK/T细胞淋巴瘤治疗方法和预后分析

目的 探讨不同治疗方法对早期鼻腔NK/T细胞淋巴瘤预后的影响.方法 回顾分析15年问85例ⅠE、ⅡE期鼻腔NK/T淋巴瘤放疗及CHOP为主化疗的疗效.单纯化疗(单化组)20例,放疗后±化疗(放化组)17例(单纯放疗11例),化疗后放疗(化放组)48例.生存率计算采用Kaplan-Meier法,并Logrank法检验,Cox回归模型进行多因素分析.结果 全组5年生存率为40%,单化纽、放化组和化放组的分别为13%、54%和47%,放化纽和化放组均优于单化组(P=0.030和0.049).ⅠE局限组与超腔组的5年生存率分别为57%与28%(χ2=8.87,P=0.003),ⅡE期的为23%,与ⅠE超腔组相似(χ2=0.19,P=0.664).近期疗效达到完全缓解与未完全缓解的5年生存率分别为58%与12%(χ2=30.68,P=0.000).放疗剂量≤50 Gy与>50 Gy的完全缓解率分别为56%和86%(χ2=6.11,P=0.013),5年无复发生存率分别为89%与84%(χ2=0.36,P=0.551).首程化疗的68例中≤2、3～4、≥5个疗程者分别为18、20、30例,完全缓解率分别为0%、20%、33%(χ2=7.65,P=0.022).首程先化疗且≥3个疗程的50例和先放疗≥40 Gy的17例的完全缓解率分别为28%和88%(χ2=18.75,P=0.000).结节型和溃疡型的完全缓解率放疗均优于化疗(100%:38%,2X=7.92,P=0.005和100%:11%,χ2=14.40,P=0.000).多因素分析显示临床分期和近期疗效是影响预后的独立因素.结论 早期鼻腔NK/T细胞淋巴瘤首程应选择50 Gy放疗为宜.对于ⅠE期超腔与ⅡE期应酌情联合化疗,但CHOP方案效果欠佳.     

Neoadjuvant Chemotherapy Plus Conventional Radiotherapy or Accelerated Hyperfractionation in Stage III and IV Nasopharyngeal Carcinoma - A Phase II Study

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no response or minor partial response (15% and 18%, p = 0.009 and 0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95% CI, 0.15?2.83; p = 0.186). With a median follow-up period of 55 months (range 4?120), the 5-year disease-free interval and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval=0.71; 95% CI, 0.27?1.88; p = 0.198 and HR for overall survival = 0.81; 95% CI, 0.37?1.78; p = 0.433). The overall treatment failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main cause of treatment failure in NPC.     

Involved-field radiotherapy for patients in partial remission after chemotherapy for advanced Hodgkin's lymphoma

PURPOSE: The use of radiotherapy in patients with advanced Hodgkin's lymphoma (HL) is controversial. The purpose of this study was to describe the role of radiotherapy in patients with advanced HL who were in partial remission (PR) after chemotherapy. METHODS: In a prospective randomized trial, patients <70 years old with previously untreated Stage III-IV HL were treated with six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycine, vinblastine hybrid chemotherapy. Patients in complete remission (CR) after chemotherapy were randomized between no further treatment and involved-field radiotherapy (IF-RT). Those in PR after six cycles received IF-RT (30 Gy to originally involved nodal areas and 18-24 Gy to extranodal sites with or without a boost). RESULTS: Of 739 enrolled patients, 57% were in CR and 33% in PR after chemotherapy. The median follow-up was 7.8 years. Patients in PR had bulky mediastinal involvement significantly more often than did those in CR after chemotherapy. The 8-year event-free survival and overall survival rate for the 227 patients in PR who received IF-RT was 76% and 84%, respectively. These rates were not significantly different from those for CR patients who received IF-RT (73% and 78%) or for those in CR who did not receive IF-RT (77% and 85%). The incidence of second malignancies in patients in PR who were treated with IF-RT was similar to that in nonirradiated patients. CONCLUSION: Patients in PR after six cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicine, bleomycine, vinblastine treated with IF-RT had 8-year event-free survival and overall survival rates similar to those of patients in CR, suggesting a definite role for RT in these patients.     

Combined-modality treatment of small-cell lung cancer: Randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research(SAKK) performed a randomised phase HI trial in patients withsmall-cell lung cancer with the objective of improving the resultsof induction chemotherapy and defining the role of consolidatingchest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin,etoposide and cisplatin given every four weeks for four cycles),EVA (cyclophospha-mide, etoposide and adriamycin given everyfour weeks for four cycles) or MOC/AVP (methotrexate, vincristine,cyclo-phosphamide alternating with adriamycin, etoposide andcisplatin given for two cycles). All patients received prophylacticcranial irradiation with 30 Gy, and after four months of inductionchemotherapy were randomized to maintenance chemotherapy withor without consolidating chest irradiation. The patients inthe combined-modality maintenance arm first received radiationtherapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall responserate of 70% with 21% of complete remissions, a median survivalof 9.3 months and survival of 8% of the patients at two yearswere observed. The highest objective response rate was achievedwith the AVP-induction chemotherapy with an 80% response rateand 32% complete remissions. Similar results were achieved withthe alternating regimen of MOC/AVP. In contrast, patients treatedwith the EVA induction regimen had significantly lower overallremission (56%) and complete remission rates (7%). The roleof consolidating chest irradiation could not be clarified inlimited-disease patients due to the small number of them whowere randomised to the maintenance part of the study. However,in patients with extensive disease in partial remission afterinduction treatment, combined maintenance therapy had a moresignificant adverse effect on survival than maintenance chemotherapyalone (median survival in the maintenance phase of 148 daysversus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide andcisplatin is an active induction treatment. Consolidating chestirradiation is contraindicated in patients with extensive diseasein partial remission after induction when given in a sequentialmanner, as in our trial. small-cell lung cancer, chemotherapy, alternating chemotherapy, combined-modality treatment, radiotherapy     

根治术后盆腔复发直肠癌疗效及预后因素分析

目的 分析直肠癌根治术后盆腔复发规律以及放疗疗效和影响预后的因素.方法 回顾分析2000-2006年直肠癌根治术后盆腔复发接受放疗患者93例,分别为单纯放疗21例、放化疗56例、放疗结合手术和(或)化疗16例.放疗采用60Co或加速器X线,中位剂量59.4Gy,其中90例采用常规分割技术.68例患者放疗后接受了1～8个(中位数3个)疗程化疗,42例行同步放化疗,多为氟尿嘧啶为主的化疗方案.16例患者在放疗后接受了复发灶切除术,其中RO切除7例,姑息性肿块切除9例.结果 全组共132处复发,常见复发部位为直肠周围(31.8%)和骶前区(30.3%),髂外淋巴结和腹股沟淋巴结少见(1.5%和3.0%).总随访率为92%,随访满2、5年者分别为39、4例.有局部症状的84例患者中83%(70例)放疗后症状缓解.全组2、5年局部无进展率分别为49%、22%,2、5年生存率分别为46%、14%.多因素分析结果显示复发后治疗方法是影响直肠癌根治术后复发的局部无进展率的独立预后因素,复发灶最大径、无病间期、放疗后有无远处转移是影响直肠癌根治术后复发患者生存率的独立顶后因素.结论 直肠周围区、骶前区、髂内淋巴结区是直肠癌主要复发部位;放疗可明显改善直肠癌根治术后盆腔复发患者的症状和提高生存质量,放疗联合手术和(或)化疗可提高直肠癌根治术后复发的局部无进展率,复发灶直径＞5 cm、无病间期＜2年、放疗后有远处转移是影响预后的因素.     

Controlled trial of twelve versus six courses of chemotherapy in the treatment of small-cell lung cancer. Report to the Medical Research Council by its Lung Cancer Working Party.

A total of 497 patients with histologically or cytologically confirmed small-cell lung cancer were prescribed initial treatment with six courses of etoposide, cyclophosphamide, methotrexate and vincristine at 3-week intervals. Patients with limited disease (74% of the total) also received radiotherapy (40 Gy in 15 fractions in 3 weeks) to the primary site between courses 2 and 3. At the end of this initial treatment, 265 patients still in complete or partial response were randomly allocated to six further courses of maintenance chemotherapy (M series: 131 patients) or to no maintenance chemotherapy (NoM series: 134 patients). Response, as assessed 3 weeks after the second course of initial chemotherapy, was achieved in 85% of the 264 patients assessed, a complete response in 11%. The median survival period from the date of start of chemotherapy was 39 weeks; 154 (31%) of the patients were alive at 1 year, 29 (6%) at 2 years and 17 (3%) at 3 years. The patients'' general condition and extent of disease pretreatment correlated significantly with survival. Among the 131 M and 134 NoM patients there was no overall survival advantage to either series (P = 0.27, log rank test), although in 99 patients who had a complete response to initial chemotherapy as assessed at the time of randomisation there was a suggestion that survival was longer in the M series (P less than 0.05, log rank test), the median survival periods from the date of randomisation being 42 weeks for the M and 30 weeks for the NoM patients. Maintenance chemotherapy was associated with additional toxicity and a poorer quality of life as assessed intermittently by clinicians and daily by patients. In conclusion, no worthwhile clinical advantage was achieved by the policy of continuing chemotherapy beyond six courses, except possibly in patients with a complete response to the initial six courses.