TP与EC-T新辅助化疗方案治疗三阴性乳腺癌的pCR率及不良反应比较

目的比较TP(紫杉醇+卡铂)与EC-T(表柔比星+环磷酰胺序贯紫杉醇)新辅助化疗(NAC)方案治疗三阴性乳腺癌(TNBC)的病理学完全缓解(pCR)率及临床不良反应。方法回顾性分析我院收治的126例TNBC患者的临床资料,应用TP方案的患者为观察组(n=65),应用EC-T方案的患者为对照组(n=61)。观察组与对照组均行8周期化疗,术后评估pCR率及临床不良反应发生情况。结果观察组的pCR率为33.85%,高于对照组的16.39%(P<0.05)。两组患者的各项不良反应发生率比较,差异均无统计学意义(P>0.05)。结论TNBC患者术前NAC应用TP方案治疗,pCR率明显优于EC-T方案,不良反应发生率无明显增加,值得临床应用。     

Preoperative second-line chemotherapy induces objective responses in primary breast cancer

Summary PURPOSE: Preoperative chemotherapy in patients with primary breast cancer results in high response rates, allowing breast-conserving surgery in patients primarily not suitable for this procedure. Tumors of patients with histologically proven breast cancer that fail to respond to preoperative chemotherapy are thought to be chemotherapy resistant. We questioned this hypothesis and treated 13 patients who did not respond to preoperative anthracycline-containing first-line treatment. PATIENTS AND METHODS: Eight patients received a combination therapy consisting of epidoxorubicin and docetaxel as neoadjuvant first-line treatment and were treated with CMF as preoperative second-line chemotherapy. The other five patients did not respond to first-line FEC and were given paclitaxel or docetaxel as second-line treatment. RESULTS: A major response to treatment was observed in 10 of 13 patients (77%) during preoperative second-line therapy: one patient (8%) achieved pathological complete response (pCR) and nine patients (69%) partial response (PR). Three patients (23%) had stable disease (SD), and no patient had progressive disease (PD). Eight patients (62%) could undergo breast-conserving surgery. CONCLUSIONS: We conclude that it is possible to achieve objective responses including pCR with potentially non-cross-resistant neoadjuvant second-line therapy, leading to breast-conserving surgery in a high proportion of patients. Thus, preoperative second-line chemotherapy appears to be justified when breast conservation is an important treatment goal and may have potential in improved tailoring of neoadjuvant treatments.     

Mid-treatment Ultrasound Descriptors as Qualitative Imaging Biomarkers of Pathologic Complete Response in Patients with Triple-Negative Breast Cancer

This study aimed to investigate mid-treatment breast tumor ultrasound characteristics that may predict eventual pathologic complete response (pCR) in triple-negative breast cancer; specifically, we examined associations between pCR and two parameters: tumor response pattern and tumor appearance. Ultrasound was performed at mid-treatment, defined as the completion of four cycles of anthracycline-based chemotherapy and before receiving taxane-based chemotherapy. Consensus imaging review was performed while blinded to pathology results (i.e., pCR/non-pCR) from surgery. Tumor response pattern was described as “complete,” “concentric,” “fragmented,” “stable” or “progression.” Tumor appearance was designated as “mass,” “architectural distortion,” “flat tumor bed” or “clip only.” Univariate and multivariate regression analyses of 144 participants showed significant associations between mid-treatment response pattern and pCR (p = 0.0348 and p = 0.0173, respectively), with complete and concentric response patterns more likely to achieve pCR than other patterns. Univariate and multivariate regression analyses further showed significant associations between mid-treatment tumor appearance and pCR (p < 0.0001 for both), with persistent appearance of mass less likely than other appearances to achieve pCR. To conclude, our study demonstrated strong associations between pCR and both tumor response pattern and tumor appearance, thereby suggesting that these parameters have potential as qualitative imaging biomarkers of pCR in triple-negative breast cancer.     

Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1-4, N0-2, M0)

BACKGROUND: Preoperative (neo-adjuvant) chemotherapy is very effective in downstaging primary tumors and moreover is able to prevent advancing metastatic growth early in the course of the disease. METHODS: We report on 38 patients with a median age of 54 years (range, 33-70 years) suffering from biopsy-proven breast cancer (T1-T4). Mastectomy had been considered the treatment of choice in all cases. The patients received 194 cycles of chemotherapy with docetaxel (75 mg/m2) and epidoxorubicin (75 mg/m2) on day 1, every 21 days, together with 30 million IU of G-CSF from days 3 to 10. Three to 8 cycles (median 5 cycles) of the treatment were administered until best response was achieved on mammography and clinical assessment. RESULTS: The neo-adjuvant chemotherapy was well tolerated and all patients completed the treatment regimen on an out-patient basis. During 194 cycles we observed leukopenia WHO grade IV only at one occasion (0.5%). WHO-grade III toxicity consisted of leukopenia (0.5%), diarrhoea (2%), and stomatitis (0.5%). Response to treatment was present in 85%, with 4 patients (11%) experiencing a pathological complete response (pCR) of the invasive tumor (T0: n = 2, DCIS: n = 2) and 28 patients (74%) showing a partial pathological response. In 21 patients (52%) a breast-conserving surgical procedure was possible. SUMMARY: We conclude that neo-adjuvant treatment of primary breast cancer with docetaxel and epidoxorubicin is safe and effective. By applying more chemotherapy cycles preoperatively it might even be possible to raise the rate of pCR and prolong survival.     

剂量密度化疗在乳腺癌辅助化疗中的随机对比研究

目的观察剂量密度化疗治疗乳腺癌的不良反应及对无病生存期和总生存期的影响。方法对40例腋窝淋巴结转移≥4个的乳腺癌术后患者随机分为治疗组和对照组,治疗组给予由表阿霉素、5-氟脲嘧啶、环磷酰胺3药组成的每2周间隔给药的序贯剂量密度辅助化疗;对照组给予每3周间隔给药的常规FEC方案化疗;主要观察治疗组的不良反应及对无病生存期和总生存期的影响。结果治疗组和对照组的不良反应类型相似,主要有恶心、呕吐、脱发、白细胞减少、口腔溃疡及肝功能异常。治疗组和对照组相比Ⅲ~Ⅳ度白细胞减少的发生率为31.6%和9.5%,治疗组高于对照组,但无统计学差异;治疗组中有1例发生中性粒细胞减少性发热。其余的毒性反应两组无明显差异。两组均完成了全部化疗,无治疗相关性死亡。中位随访时间26个月,治疗组和对照组的中位无病生存期、1年、2年DFS分别为26个月、100%、73.7%和20个月、95.2%、71.4%;治疗组和对照组的1、2年生存率均为100%。治疗组的中位无病生存期、1年及2年DFS优于对照组。结论患者对本研究中的序贯剂量密度化疗方案的耐受性良好,初步结果显示,剂量密度化疗对腋窝淋巴结转移≥4个的乳腺癌术后患者可能有更好的生存优势。     

乳腺癌新辅助化疗疗效的影响因素分析

目的探讨影响乳腺癌新辅助化疗(NAC)疗效的影响因素。方法 120例接受NAC的乳腺癌患者,采用免疫组化法确定雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体-2(HER-2)和Ki-67状态,并分析相关病历资料,Logistic回归分析患者达到病理完全缓解(p CR)的影响因素。结果 17例患者达到p CR,占14.2%。单因素分析结果显示,肿瘤大小、ER、PR和化疗方案为影响疗效达到p CR的相关因素。多元Logistic回归分析结果显示,肿瘤大小为影响疗效达到p CR的独立危险因素。结论乳腺癌NAC p CR与肿瘤大小、ER、PR和化疗方案等因素有关,其中肿瘤大小是其独立危险因素。     

Correlation between the in vitro ATP-based chemosensitivity assay and HER2/neu expression in women with breast cancer

Several in vitro chemosensitivity tests have been developed to predict the chemotherapeutic response of tumours prior to initiation of individualized treatment for breast cancer. This study investigated whether the in vitro chemosensitivity response of cell lines derived from breast cancer patients was affected by HER2/neu expression. We cultured breast cancer cell lines from 50 patients and the adenosine triphosphatebased chemotherapy response assay (ATPCRA) was performed with 5-fluorouracil, gemcitabine, docetaxel, doxorubicin, methotrexate, vinorelbine and paclitaxel. 5-fluorouracil combined a high median cell death rate (32.4%) with the narrowest range of cytotoxic effects (7.3-65.7%). In addition, gemcitabine showed significantly greater activity in HER2/neupositive patients. In contrast, docetaxel was significantly less effective in HER2/neu-positive patients. No significant correlation was found between the other agents and HER2/neu expression. The use of the ATP-CRA test for metastatic tissue from patients with recurrent disease might be a useful approach to determine the most effective chemotherapy regimen.     

Oral chemotherapy with idarubicin plus cyclophosphamide in advanced breast cancer.

An oral chemotherapy schedule based on idarubicin and cyclophosphamide was evaluated in 31 advanced breast cancer patients. Out of 27 patients evaluable for response, 1 (3.7%) achieved a complete response and 5 (18.5%) a partial response, with an objective response rate of 22.2% (95% confidence limits 8.6-42.3%). The median time to progression was 7 months (range 3-12). Fourteen patients (51.9%) showed a disease stabilization, and 7 progressed (25.9%). Toxicity was mild. Considering the low response rate, but also the advantages of oral chemotherapy and the mild toxicity observed, oral idarubicin plus cyclophosphamide can be considered as a second-choice regimen in advanced breast cancer.     

Acute and anticipatory emesis in breast cancer patients

A group of 90 breast cancer patients undergoing chemotherapy were assessed prospectively to estimate the prevalence of acute (post-treatment) and anticipatory emesis in the 1990s. For this purpose, two protocols of chemotherapy were analysed separately: cyclophosphamide/methotrexate/5-fluorouracil (CMF) and 5-fluorouracil/doxorubicin/cyclophosphamide (FAC). All patients were treated with antiemetic therapy, which included one corticoid plus ondansetron (in the FAC regimen), or one corticoid plus thiethylperazine (in the CMF regimen). For at least one cycle of chemotherapy 86.1% and 91.7% patients in the FAC protocol presented vomiting and nausea respectively; 11.1% had anticipatory vomiting and 30.6% had anticipatory nausea. In the CMF protocol, 79.6% had post-chemotherapy vomiting and 71.7% had post-chemotherapy nausea associated with at least one cycle. In this group, 7.4% had anticipatory vomiting and 16.6% had anticipatory nausea. A high proportion of patients suffered anticipatory anxiety in both groups (75% in FAC, 74.1% in CMF). The stimuli most frequently associated with the appearance of anticipatory emesis were olfactory stimuli and cognitive stimuli. In summary, as a result of the advances made in antiemetic control during the last decade, the severity of chemotherapy-induced emesis seems to have significantly decreased, but the prevalence of these symptoms along the course of the treatment still remains high.     

超声结合钼靶成像及Ki-67表达对乳腺癌新辅助化疗疗效的预测价值

目的 探讨常规超声、钼靶X线影像学特征及Ki-67阳性表达率对乳腺癌新辅助化疗后达到病理完全缓解(pCR)的预测价值.方法 回顾性选取2014年11月至2019年11月在常州市第二人民医院行新辅助化疗治疗的68例乳腺癌患者,患者行化疗前均接受乳腺超声和钼靶X线检查,且均经粗针穿刺取得病理和免疫组化结果.依据新辅助化疗疗...     

紫杉醇联合顺铂治疗78例晚期乳腺癌的近期疗效

目的：评价紫杉醇联合顺铂对晚期乳腺癌的治疗作用。方法：采用紫杉醇联合顺铂的联合方案，治疗晚期乳腺癌78例，均为初治患者，均经细胞学或病理证实。结果：本组完全缓解CR10．3％8例，部分缓解PR53．8％42例，(CR PR)有效率64％。主要毒性为骨髓抑制及消化道反应、结论：紫杉醇联合顺铂方案是治疗晚期乳腺癌较为理想的方案。     

Treatment of Borrmann type IV gastric cancer with a neoadjuvant chemotherapy combination of docetaxel, cisplatin and 5-fluorouracil/leucovorin

This study evaluated the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil/leucovorin as neoadjuvant chemotherapy before surgery (NCT group; n = 29) compared with postoperative chemotherapy alone (non-NCT group; n = 26) in the treatment of Borrmann type IV gastric carcinoma. Primary tumour response rate, surgical parameters, incised-edge residue rate, lymphatic metastasis status and side-effects were evaluated. The overall response rate was 58.6% in the NCT group, which included three (10.3%) patients in complete remission and 14 (48.3%) patients in partial remission. The postoperative pathological complete response rate was 6.9% (two patients) in the NCT group. NCT was associated with a significant increase in the radical resection rate and a significant decrease in the rate of incised-edge residues, compared with postoperative chemotherapy alone. Side-effects due to NCT were minimal and resolved with appropriate treatment. There were no chemotherapy-related deaths in either group. In conclusion, docetaxel, cisplatin and 5-fluorouracil/leucovorin was an effective and well-tolerated NCT regimen for Borrmann type IV gastric cancer.     

紫杉醇为主化学治疗方案治疗中晚期胃癌的临床疗效分析

目的：探讨脂质体紫杉醇联合顺铂、氟尿嘧啶和奥沙利铂联合氟尿嘧啶的化学治疗方案治疗中晚期胃癌的临床疗效及其不良反应。方法选取94例中晚期胃癌患者,随机分为研究组和对照组,每组各47例,研究组采用脂质体紫杉醇联合顺铂、氟尿嘧啶的化学治疗方案,对照组采用奥沙利铂联合氟尿嘧啶化学治疗方案,所有患者至少行化学治疗2个周期,化学治疗2～6个周期后评价其临床疗效及其不良反应。结果两组的客观反应率（ORR）分别为53％和49％,疾病控制率（DCR）分别为79％和74％,2组在ORR、DCR、中位生存期以及1年生存率方面比较差异均无统计学意义（P均＞0．05）。研究组的不良反应主要为脱发以及血液学毒性,而对照组的不良反应主要为外周神经毒性,均可耐受,不影响继续治疗。结论以脂质体紫杉醇为主的联合化学治疗方案治疗中晚期胃癌取得了较好的近期和远期疗效,且患者对毒副作用均可以耐受。     

Autologous stem cell transplantation following induction therapy with an anthracycline-based regimen including interferon-alpha for low-grade non-Hodgkin's lymphoma

The role of upfront autologous stem cell transplantation (ASCT) in low-grade non-Hodgkin's lymphoma (LGNHL) continues to be an area of investigation. After undergoing this novel anthracycline-based induction regimen including interferon (IFN)-alpha, a group of LGNHL patients received high-dose chemotherapy followed by ASCT. The induction regimen was based on the concept of regrowth resistance in which patients received nonmyelotoxic agents mid-cycle to slow tumor proliferation between courses of cytotoxic therapy. In addition, IFN-alpha was given at the end of the cycle because studies have shown that it has a 50% response rate in treating LGNHL. We treated 44 consecutive patients between August 1993 and February 1999 with an induction regimen containing cyclophosphamide, mitoxantrone, and teniposide intravenously on day 1 with oral prednisone given on days 1-5. On day 15, patients received vincristine and bleomycin IV. IFN-alpha-2b subcutaneously was administered on days 22-26. In this phase II single-institution study, there were 2 main patient groups. Nineteen patients received the chemotherapy induction regimen and 17 patients received chemotherapy followed by upfront ASCT. For the chemotherapy group, 58% had follicular histology and 84% had stage IV disease. For the ASCT group, 76% had follicular histology, and 71% had stage IV disease. Of the patients treated with chemotherapy, the overall response rate was 95% with 58% complete responses and 37% partial responses. Of the patients treated with chemotherapy and later ASCT, the overall response rate was 100% with 82% complete responses and 18% partial responses. In analyzing progression-free curves for these 2 groups of patients, there was evidence that the upfront autologous group fared better, log-rank test X(2)=4.6028, P < .0319.     

Long-term remission in a patient with carcinoma of unknown primary site

BACKGROUND: Cancer of unknown primary site also designated as CUP syndrome usually presents as metastatic disease with a poor prognosis and low remission as well as survival rates. CASE: We report a 46-year-old male with para-aortal and left-sided cervical lymph node metastases. Histological examination of a cervical lymph node revealed papillary carcinoma. Despite thorough investigation, no primary tumor was found. The patient was empirically treated with six courses of the FACP regimen (5-fluorouracil, Adriamycin, cyclophosphamide and cisplatin) combined with radiotherapy (40 Gy) and has remained in complete remission for 124 months. CONCLUSION: This case indicates that treatment of a patient with cancer of unknown primary site may be rewarded by a benign course. However, complete cure remains a very rare event in CUP. Remission can be achieved with a platinum-containing regimen combined with radiotherapy.     

Antiemetic activity of megestrol acetate in patients receiving chemotherapy

Purpose

Several trials had independently noted that patients receiving megestrol acetate had less nausea and vomiting, but this antiemetic activity of megestrol acetate has not been reported separately in the literature. Our objective was to evaluate the antiemetic ability of megestrol acetate in patients receiving chemotherapy.

Patients and Methods

Patients receiving chemotherapy were randomly assigned to receive either megestrol acetate 320?mg PO or placebo before the first day of chemotherapy, followed on days 1?C4 by megestrol acetate 320?mg PO combined with granisetron 3?mg IV and metoclopramide 20?mg IM or only granisetron 3?mg IV combined with metoclopramide 20?mg IM in a crossover manner during two consecutive cycles. Rates of complete protection against both vomiting and moderate-to-severe nausea was the primary end point.

Results

One hundred patients were enrolled in the study. The antiemetic regimen containing megestrol acetate was superior in providing complete protection from nausea and vomiting (45% megestrol acetate regimen vs.17% no megestrol acetate regimen). Complete response of acute phase in both antiemetic regimens was different (85% megestrol acetate regimen vs. 72% no megestrol acetate regimen). Complete response of delayed emesis was also different (49% megestrol acetate regimen vs. 18% no megestrol acetate regimen). Adverse events were mostly mild to moderate. There were no serious drug-related adverse events between the two antiemetic regimens.

Conclusion

Megestrol acetate was shown to be an effective antiemetic agent. Megestrol acetate might be a new antiemetic option for chemotherapy.     

A study of weekly paclitaxel plus 5-fluorouracil and cisplatin for patients with advanced or recurrent inoperable gastric cancer

Purpose

To investigate the efficacy and safety of weekly paclitaxel plus 5-fluorouracil and cisplatin for patients with advanced or recurrent inoperable gastric cancer.

Patients and methods

The eligibility criteria included histologically confirmed advanced gastric cancer or recurrent inoperable gastric cancer. Patients were treated with weekly paclitaxel 60 mg/m² on the 1st, 8th and 15th days combined with 5-fluorouracil 500 mg/m² by a continuous intravenous infusion from the 1st to the 5th day, and a cisplatin 75 mg/m² intravenous infusion for 3 days. The cycles were repeated every 4 weeks.

Results

Forty-six patients were assessed for response and toxicity. Three patients achieved complete responses, and 20 patients achieved partial responses; the overall response rate was 50.0% (95% confidence interval [CI], 34.9–65.1%). With a median follow-up of 20 months, the median progression-free and overall survivals were 24 and 46 weeks, respectively, with a 1-year survival rate of 41.3% (95% CI, 27.0–56.8%). The most common hematological toxicity was myelosuppression, which included neutropenia, anemia, thrombocytopenia; the grade 3 toxicity rate was 26.1% (12/46), and only 1 patient was observed with a grade 4 neutropenia. The nonhematological toxicities included anorexia, diarrhea, nausea/vomiting, stomatitis/mucositis, alopecia, dizziness, skin rash, neurotoxicity, and infection; the grade 3 toxicity rate was 34.8% (16/46), but no grade 4 nonhematologic toxicity was observed.

Conclusions

The combination chemotherapy consisting of weekly paclitaxel plus 5-fluorouracil and cisplatin was effective and well tolerated in patients with advanced and recurrent inoperable gastric cancers.     

Control of emsis by intravenous granisetron in breast cancer patients treated with 5-FU,epirubicin and cyclophosphamide

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT₃) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0–2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%–98% and 77%–93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect folloed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.