Dose-intense ifosfamide/doxorubicin/cisplatin based chemotherapy for osteosarcoma in adults

The efficacy of neoadjuvant and adjuvant chemotherapy has been clearly established in the treatment of osteosarcoma; however, the most active regimen remains to be identified. This prospective study evaluated the efficacy and toxicity of a dose-intense ifosfamide, doxorubicin, and cisplatin-based neoadjuvant regimen in adults with osteosarcoma. We prospectively treated 20 patients with osteogenic sarcoma with two cycles of ifosfamide/doxorubicin followed by two cycles of doxorubicin/cisplatin every 2 weeks. Surgical specimens were analyzed for percent tumor necrosis. Patients who demonstrated a "good response" (GR) to chemotherapy received the same combination postoperatively at a lower dose rate. Patients who demonstrated a "poor response" (PR) received four cycles of high-dose methotrexate alternating with two cycles of ifosfamide/etoposide and two cycles of cisplatin/etoposide after the surgery. Neoadjuvant chemotherapy was well tolerated with moderate hematologic toxicity. Twelve of 19 evaluable patients (63%) were treated according to the GR arm and 7 according to the PR arm. At median follow-up of 5.5 years, disease-free survival (DFS) and overall survival (OS) are 68% and 74%, respectively. Patients treated on the GR arm had DFS and OS of 75% and 83%, respectively, whereas patients on the PR arm had DFS and OS of 57%. Intensive neoadjuvant chemotherapy is effective and moderately well tolerated in patients with de novo osteosarcoma. The outcome data suggest that lack of a near complete response to preoperative chemotherapy reflects inherent biologic resistance to chemotherapy and hence a poor prognosis.     

吉西他滨联合洛铂与联合顺铂方案治疗术后辅助化疗失败的卵巢癌患者的疗效对比

目的:观察吉西他滨联合洛铂与联合顺铂方案治疗术后辅助化疗失败的卵巢癌患者的疗效及安全性。方法:自2011年6月21日至2016年5月30日,我科收治的初治失败的卵巢癌患者共73例入组,随机分为吉西他滨联合洛铂组（GL组）与吉西他滨联合顺铂组（GP组）,比较两方案在平均化疗周期数、总有效率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）及不良反应发生率等方面的差异。结果:两组患者的平均化疗周期数GL组（4.73±1.305）周期,GP组(4.03±1.341)周期,P=0.027,差异有统计学意义。ORR、DCR间的比较差异均无统计学意义（P=0.345;P=0.127）。GL组中位PFS为6.0个月（95%可信区间5.722~6.278个月）,GP组5.0个月（95%可信区间4.209~5.791个月）,P=0.414,无统计学差异。GL组中位OS为10.0个月（95%可信区间8.675~11.325个月）,GP组9.0个月（95%可信区间8.296~9.704个月）,P=0.308,无统计学差异。不良反应中,GL组轻中度血小板降低较多（P=0.006）,GP组有较多的轻中度肝功能异常（P=0.007）、中重度恶心（P=0.043）及中重度呕吐（P=0.019）。其余不良反应两组间无统计学差异。结论:GL方案对于初治失败的卵巢癌患者而言是安全有效的,可达到与GP方案类似的治疗效果,不良反应较GP方案轻,但需要注意血小板降低。     

Postoperative adjuvant intraarterial chemotherapy of combined cisplatin and 5-FU for advanced hepatocellular carcinoma

Postoperative adjuvant intraarterial infusion chemotherapy was performed for 22 hepatectomized patients with Stage III and Stage IV-A hepatocellular carcinoma from July, 1997, to December, 1999. One course of this chemotherapy consisted of cisplatin (10 mg/body/day on days 1-5) followed by 5-FU (250 mg/body/day on days 1-5). One hundred forty-eight patients of Stage III and Stage IV-A underwent hepatectomy from 1992 to 2001 and were enrolled as historical control. There were 9 Stage III cases treated with this adjuvant chemotherapy, and there were 7 or 6 Stage IV-A cases with and without main portal thrombosis, respectively. Survival and disease-free survival curves were not improved compared to historical control by this adjuvant chemotherapy. The number of recurrences in the remnant liver of 2 Stage IV-A cases with main portal thrombosis was limited to 3. Those cases treated with rehepatectomy and transarterial chemoembolization survived about 1,200 days without tumor recurrence.     

Etoposide, cyclophosphamide, cisplatin, and doxorubicin as neoadjuvant chemotherapy for osteosarcoma

The authors evaluated the combination of etoposide/cyclophosphamide (VP/CY) as initial, presurgical therapy for patients with osteosarcoma and found an 88% response rate for the primary tumor and any metastases. After definitive, limb-salvage surgery and adjuvant chemotherapy with etoposide, cyclophosphamide, cisplatin, and doxorubicin, patients without metastases at diagnosis whose cases were followed for a median of 2 years from diagnosis achieved a relapse-free survival (RFS) probability of 78% +/- 9%. This result is equivalent to the best adjuvant chemotherapy results reported to date. Patients without metastases at diagnosis had significantly better RFS probability (78% +/- 9%) than those with metastases at diagnosis (0%). Transient, severe myelosuppression has been the only major toxicity of the VP/CY courses. No irreversible organ damage or toxic deaths have been seen in patients enrolled in this study. The authors conclude that the combination of VP/CY is effective treatment for osteosarcoma, and when combined with cisplatin/doxorubicin (CIS/DOX), is as effective as any previously reported chemotherapy for osteosarcoma.     

First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

Background:

Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as ^99mTc-LD distribution in MPM lesions after chemotherapy administration.

Methods:

A total of 38 patients with non-resectable MPM received LD 40 mg m⁻² and cisplatin 60 mg m⁻² every 21 days. Gamma camera images of ^99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials ({"type":"clinical-trial","attrs":{"text":"NCT00886028","term_id":"NCT00886028"}}NCT00886028).

Results:

In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001).

Conclusion:

The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. ^99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues.     

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.     

SFOP OS94: a randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients

The SFOP-OS94 randomised multi-centre trial was designed to determine whether preoperative chemotherapy regimen combining high-dose methotrexate courses and etoposide-ifosfamide could improve the proportion of good histologic response (5% viable cells) compared to a regimen based on high-dose methotrexate and doxorubicin, in children/adolescents with localised high-grade limb osteosarcoma. Postoperative chemotherapy was adapted to the histologic response. Overall, 234 patients were randomised between 1994 and 2001. There were 56% good responders in the etoposide-ifosfamide arm versus 39% in the doxorubicin arm (p-value=0.009). With a median follow-up of 77 months, the 5-year event-free survival of the entire population was 62%, slightly greater in the etoposide-ifosfamide arm than in the doxorubicin arm, but the difference was not significant (Hazard Ratio: HR=0.71, 95%CI: 0.5-1.06, p-value=0.09). Five-year overall survival of the entire population was 76%, similar in both arms (HR=0.95, 95%CI: 0.6-1.6, p-value=0.85). Toxicity was manageable with different acute toxicity profiles between treatment arms. No acute toxicity related death was reported. About 43% of the patients in the etoposide-ifosfamide arm were event-free at 3 years without having received any doxorubicin or cisplatin, thus avoiding the risk of long-term cardio- and ototoxicity.     

A feasibility study of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer

OBJECTIVE: We evaluated the feasibility of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer. METHODS: Patients with newly diagnosed advanced endometrial cancer received AP (doxorubicin 60 mg/m(2), cisplatin 50 mg/m(2)) every 3 weeks. Treatment was continued until disease progression or completion of 6 courses. Toxicities were evaluated every cycle according to NCI-CTCAE Ver.3.0. RESULTS: Fifteen patients were enrolled from April 2004 through December 2005. All patients successfully completed therapy. There were two patients who needed dose reduction and nine patients with prolongation of treatment interval. Patients with over Grade 3/4 toxicity were observed to have leucopenia (47%), neutropenia (67%), anemia (26%), and vomiting (13%). No grade 3/4 cardiac and renal failure were observed. CONCLUSIONS: The doxorubicin/cisplatin (AP) regimen is tolerated and can be safely given without severe toxicity.     

Effect of preoperative chemotherapy by intraarterial infusion of cisplatin (cis-dichlorodiammineplatin) on primary osteosarcomas

Preoperative chemotherapy was conducted in seven cases of osteosarcoma by twice administering intraarterial infusions of cisplatin (100 mg/m2/day) and the effects were studied through evaluations of clinical symptoms, plane radiograms, angiographic findings, serum alkaline phosphatase levels determined prior to and after the intraarterial infusion, and the rate of necrosis of tumor cells in the resected material. Results of treatment were as follows: disappearance of pain in two cases; reduction of pain in five cases; reduction in tumor size in three cases; and an increase in tumor size in one case. Radiograms obtained after treatment showed a reduction of tumor shadow at the extraskeletal site in one case; no change in five cases; an increase in one case, a clearly defined lesion border in one case; and no change in six cases. The radiograms showed no significant change in many cases, but this is perhaps because the radiograms were taken only four weeks after the start of treatment. Angiograms obtained after the preoperative chemotherapy revealed the disappearance of neovascularity in neoplasms in three cases, reduction in two cases, and no change in two cases. Reductions in the rates of serum alkaline phosphatase levels were in the range of 8.3 to 93% (average, 47.8%); the rates of necrosis of the tumor cells in the resected materials were ranged from 53 to 95% (average, 82.1%). The present chemotherapy resulted in formation of a fibrous connective tissue in the reactive zone and in increase in thickness of its pseudo-capsule. From this, it may be said that, if a tumor is to be resected in the area a few of more centimeters distant from the newly formed tissue, the surgery can be conducted within a wide curative margin, or a safer surgical margin. Results obtained from an overall evaluation of the effects showed the chemotherapy to be markedly effective in one case, effective in four cases, slightly effective in one case, and to have no effect in one case. For making life prognostic evaluations, more case data and longer-range follow-up observations will be needed.     

A case of AGC with pCR after preoperative chemotherapy including S-1 plus cisplatin

A 79-year-old man complaining of epigastralgia was examined and diagnosed with advanced gastric cancer (UML, Type 5, Ant-Less-Gre, cT4a, cN1, cH0, cP1, cStage IV). A poor prognosis was predicted, but we tried preoperative chemotherapy hoping for a down-staging of the tumor. We chose a regimen of S-1 plus cisplatin as follows: S-1 (60 mg/m2) was administered orally for 3 weeks followed 2 weeks of rest, and cisplatin (50 mg/m2) was administered by intravenous drip on day 8. After three cycles of treatment, diagnostic laparoscopic examination revealed a suspected serosal invasion of the main tumor, but peritoneal dissemination was not seen, and abdominal washing cytology was negative. After the fourth cycle of treatment, total gastrectomy with lymph node dissection (D1+No. 7, 8a, 9, R0) was performed. Histological examination of the resected specimens revealed no residual cancer cells in the primary lesion or regional lymph nodes, resulting in a diagnosis of complete response to chemotherapy according to the Japanese Classification of Gastric Carcinoma. The postoperative course was uneventful, and he has been fine as an outpatient.     

Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma

Summary Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Turmors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.This work was supported by the Hamburger Krebsgesellschaft and the Bundesministerium für Forschung und Technologie     

Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer

Background

We previously reported that S-1 plus cisplatin was feasible as adjuvant chemotherapy for stage III gastric cancer after D2 gastrectomy. Herein we evaluate the recurrence-free survival and overall survival rates as secondary endpoints based on updated follow-up data.

Methods

Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Treatment consisted of 3 cycles of S-1 (40 mg/m² PO) twice daily on days 1–21 and cisplatin (60 mg/m² IV) on day 8, and S-1 was given on days 1–28 every 6 weeks until 1 year after surgery.

Results

From August 2007 to September 2009, 63 patients were accrued. Overall, 34 and 25 patients had stage IIIA and IIIB disease, respectively. After a median follow-up of 3.9 years, 16 patients experienced recurrence and 11 patients died. The 3-year recurrence-free survival rate was 74.1 % (95 % CI: 60.8–83.5 %, IIIA 81.8 %, IIIB 64.0 %). The 3-year overall survival rate was 84.5 % (95 % CI: 72.3–91.6 %, IIIA 87.9 %, IIIB 80.0 %). Recurrence sites included the peritoneum (n = 8), hematogenous sites (n = 6), and lymph nodes (n = 4).

Conclusion

The present results indicate that adjuvant therapy with S-1 plus 3 cycles of cisplatin may provide a survival benefit to patients with stage III gastric cancer.     

MMIA术前化疗在骨肉瘤保肢术中的意义

 目的　探讨以大剂量甲氨喋呤、异环磷酰胺和阿霉素组成的MMIA方案在骨肉瘤保肢术中的价值。方法　 9例骨肉瘤于术前化疗 2疗程后行保肢术 ,对比观察术前未行化疗的 2 1例骨肉瘤患者。评价化疗对保肢术的可行性及术后并发症的影响。结果　无 1例因并发症而终止化疗 ,化疗后AKP、LDH明显下降 ,7例患者的疼痛消失 ,影像学显示肿瘤明显缩小、钙化。术后标本肿瘤细胞坏死率Ⅳ级 3例 ,Ⅲ级 3例 ,Ⅱ级 2例 ,Ⅰ级 1例。术前化疗组中 1例切口延迟愈合 ,随访期间 1例复发 ,1例死亡。非化疗组 3例术后切口延迟愈合 ,随访期间 6例复发 ,7例肺转移 ,7例死亡。统计学分析发现术前化疗与术后复发有关 ,与切口愈合无关。结论　MMIA术前化疗可以在不影响切口愈合的前提下 ,扩大保肢手术适应症 ,改善手术局部控制率     

调强放射治疗联合同步及辅助替莫唑胺化疗治疗脑胶质瘤术后残余病灶的临床研究

目的:观察调强放射治疗(intensity-modulated radiation therapy,IMRT)联合同步及辅助替莫唑胺(temozolomide,TMZ)化疗治疗脑胶质瘤患者术后残余病灶的疗效和不良反应。应用放射治疗剂量学分析IMRT时肿瘤靶区剂量分布及危及器官的受照剂量。方法:研究对象为2008年4月-2009年6月共21例脑胶质瘤术后有残余病灶的患者,其中WHO病理分级Ⅱ级10例,Ⅲ～Ⅳ级11例。IMRT给予肿瘤靶区总剂量59.92～64.20Gy/28～30fx;同步化疗,替莫唑胺每天50～75mg/m2;同期放化疗结束4周后,继续替莫唑胺口服辅助化疗,每天150～200mg/m2d1～5,28d为1个化疗周期,共6个周期。结果:完全缓解2例,部分缓解17例,疾病稳定2例,有效率达90.5;其中Ⅱ级患者的有效率为100.0(10/10),Ⅲ～Ⅳ级患者的有效率为81.8(9/11)。1年无进展生存率为80.9,总生存率为85.7;其中Ⅱ级患者的1年无进展生存率和总生存率均为100.0,Ⅲ～Ⅳ级患者的1年无进展生存率和总生存率分别为72.7和81.8。各重要器官的受照剂量均明显低于常规放疗的最小耐受剂量。不良反应较轻,患者耐受良好。结论:IMRT联合同步及辅助替莫唑胺化疗治疗脑胶质瘤的近期有效率较高且不良反应较轻,可较好地保护肿瘤靶区周围重要的正常器官。     

高分级脑胶质瘤术后同步放化疗联合辅助化疗的临床研究

目的:探讨高分级脑胶质瘤术后同步放化疗联合辅助化疗的临床效果。方法:选取高分级脑胶质瘤手术患者138例,随机分为两组,使其具有可比性。对照组67例,给予单纯放射治疗。观察组71例,在对照组基础上给予同步化疗和辅助化疗。对两组患者治疗效果进行统计。随访三年,记录三年期间生存率。结果:观察组患者完全缓解、部分缓解、稳定、进展和有效率分别为47.89%、40.85%、8.45%、2.82%和88.73%,对照组分别为28.36%、32.84%、13.43%、25.37%和61.19%,观察组患者完全缓解率和有效率均明显高于对照组,两组比较差异有统计学意义（P<0.05）。观察组患者术后一年、两年、三年生存率分别为91.55%、69.01%和50.70%,对照组分别为50.75%、16.42%和10.45%,观察组明显高于对照组,两组比较差异有统计学意义（P<0.05）。观察组患者发生恶心呕吐、中性粒细胞下降以及血小板减少者分别占63.38%、49.30%和52.11%,对照组分别为62.69%、46.27%和52.24%,两组比较差异无统计学意义。结论:高分级脑胶质瘤患者在术后进行同步放化疗联合辅助化疗可以有效提高患者的治疗效果,改善患者预后,不会增加不良反应,因此是一种安全而有效的治疗方案。     

Use of doxorubicin plus cyclophosphamide followed by docetaxel as adjuvant chemotherapy for breast cancer

We evaluated the feasibility and incidence of hematological toxicity in a series of 39 breast cancer patients treated at our institute with doxorubicin plus cyclophosphamide (AC) followed by docetaxel, using prophylactic G-CSF (pegfilgrastim). We prescribed G-CSF as secondary prophylaxis during the AC regimen and as primary prophylaxis during treatment with docetaxel. For the AC treatment, we recorded 6 cases of grade III (15.3%) and one case of grade IV (2.5%) neutropenia; we found one case of Grade IV anemia. For the docetaxel regimen, we registered one case of Grade IV (2.5%) neutropenia and three cases of Grade III leukopoenia without neutropenia. No patients experienced cardiac symptoms or baseline LVEF rate decrease. All patients concluded the programmed chemotherapy. Our experience shows the safety of docetaxel in combination with anthracyclines and the efficacy of prophylaxis with G-CSF in breast cancer adjuvant chemotherapy.     

Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: results from the multiinstitutional osteosarcoma study

The multiinstitutional osteosarcoma study (MIOS), a randomized trial of adjuvant therapy for osteosarcoma with a concurrent control group, registered 113 patients from June 1982 to August 1984. Preliminary analysis of the study indicated a significant event-free survival advantage favoring immediate adjuvant chemotherapy, (P less than .001). For patients treated with surgery alone or with surgery and adjuvant chemotherapy, the lungs were involved in more than 80% of the relapses. Patients relapsing after surgery alone tended to relapse earlier (P less than .01), had more pulmonary nodules (P less than .01), and had more frequent bilateral pulmonary involvement (P less than .01) than those treated with immediate postsurgical adjuvant chemotherapy. However, patients relapsing after treatment with surgery alone experienced a significantly longer interval to further disease progression (P less than .01) and improved survival after relapse (P = .01) when compared with patients who relapsed after treatment with immediate adjuvant chemotherapy. The only factor predictive of survival after relapse was if the patient could be made surgically disease-free after initial relapse (P = .03).     

Systemic chemotherapy with high-dose cisplatin and sodium thiosulfate rescue

Intravenous bolus injection of an 80- to 120-mg/m2 dose of cisplatin followed by "rescue" with sodium thiosulfate (STS) was tried in the treatment of 7 patients with advanced tumor. STS was given continuously i.v. six hours after cisplatin injection, combined with methylprednisolone and metoclopramide as antiemetics. Four patients were evaluable, consisting of one CR, one PR and two NC. Severe nausea and emesis occurred in two patients and irreversible renal dysfunction occurred in one. The clinical use of the STS rescue regimen was discussed in conjunction with our basic investigation of "STS-rescue" in an animal model.     

吉西他滨联合顺铂治疗头颈部癌52例分析

目的 评价吉西他滨联合顺铂治疗复发转移性头颈部癌患者的疗效和毒性。方法 52例复发转移性头颈部癌患者接受吉西他滨联合顺铂方案：吉西他滨1000mg／m^2,第1天和第8天;顺铂25mg／m^2,第1～3天;21d为1个疗程。结果 可评价患者52例,3例（5．8％）达完全缓解,19例（36．5％）达部分缓解,有效率42．3％（22／52）。中位疾病进展时间5．0个月,中位生存期9．9个月,1年生存率为43．4％。在既往经含铂方案化疗的32例患者中,2例（6．3％）达完全缓解,11例（34．4％）达部分缓解,有效率为40．6％（13／32）。中位疾病进展时间3．4个月,中位生存期8．3个月,1年生存率为29．2％。主要不良反应为1或2度血液学毒性、皮疹和恶心呕吐。结论 吉西他滨联合顺铂是治疗晚期复发转移性头颈部癌患者安全、有效的联合化疗方案．     

Efficacy of combination chemotherapy with capecitabine plus cisplatin in patients with unresectable hepatocellular carcinoma

Purpose  The aim was to assess the efficacy and safety of capecitabine (X) plus cisplatin (P) in patients with hepatocellular carcinoma (HCC). Methods  We retrospectively analyzed the data of 178 assessable among 195 consecutive HCC patients ineligible for curative therapy who were treated with XP at the National Cancer Center Korea between January 2002 and July 2007. Results  One patient (0.5%) had modified UICC stage II tumors, 12 (6.7%) had stage III, 51 (28.7%) had stage IVa, and 114 (64.1%) had stage IVb. The overall response rate was 19.7%, and 45.0% achieved tumor growth control. Tumor response and disease stability were significantly higher in patients with serum α-FP < 400 ng/mL, those with CLIP score ≤ 2, and those with a uninodular intrahepatic tumor or no residual intrahepatic tumor with extrahepatic tumors alone (P < 0.05). The median time to progression (TTP) and median overall survival were 2.8 months (95% CI 2.5–3.1 months) and 10.5 months (95% CI 7.9–13.1 months), respectively. Multivariate analyses showed that a uninodular or no residual intrahepatic tumor (hazard ratio, 0.524; P = 0.006) and female gender (hazard ratio, 0.539; P = 0.019) were independent predictors affecting TTP. Gastrointestinal symptoms were the most common grade 3 and 4 toxicities. Conclusions  Although XP chemotherapy produced moderate survival outcomes in advanced HCC patients, it was efficacious in the treatment of HCC patients with a uninodular or no residual intrahepatic tumor, especially women, regardless of extrahepatic tumor status. This work was supported by National Cancer Center, Korea (Grant #0810260-1).