Search

Combination chemotherapy with pertuzumab, trastuzumab, and docetaxel is recommended as the first-line treatment for patients with HER2-positive unresectable or metastatic breast cancer. We report 2 cases of unresectable breast cancer for which pertuzumab, trastuzumab, and docetaxel therapy was effective. Case 1: A woman in her 40s was diagnosed with TxN3aM0, Stage ⅢC, HER2-positive, hormone receptor-positive advanced breast cancer. After administration of 6 courses of pertuzumab, trastuzumab, and docetaxel therapy, she underwent surgery(Bt+Ax[Ⅱ]). Histopathological examination revealed that chemotherapy effect was Grade 3. Case 2: A woman in her 60s was diagnosed with de novo Stage Ⅳ, HER2- positive, hormone receptor-negative breast cancer. She was administered 8 courses of pertuzumab, trastuzumab, and docetaxel therapy as the third-line treatment, because she initially refused treatment. Thereafter, she underwent surgery(Bt+Ax [Ⅰ]). In both cases, histopathological examination revealed complete response after chemotherapy. Thus, combination therapy of pertuzumab and trastuzumab may improve the prognosis in patients with HER2-positive breast cancer.

In the present study, we measured breath alcohol concentration(BAC)after the administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and examined the safety of OTX outpatient administration. Twenty breast cancer patients who received OTX chemotherapy at our outpatient facility were included. The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60 mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30 minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash or drunkenness due to alcohol were observed. BAC was detected in 10 cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than 0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after 30 minutes. Our results suggest that the effects of alcohol are alleviated 60 minutes after infusion and that patients receiving OTX could return home safely.

Here we present a case of breast cancer in which cardiac dysfunction had previously been observed on trastuzumab(TRS) administration; the condition then improved but reoccurred on readministration of TRS. A 52-year-old woman received preoperative chemotherapy for StageIIIC left breast cancer(fluorouracil, epirubicin and cyclophosphamide followed by docetaxel and TRS), and then underwent partial mastectomy and axillary lymph node dissection. For adjuvant therapy, she received endocrine therapy and TRS. Radiation therapy was administered to the left residual breast. The patient complained about palpitation in the 5th cycle of TRS, and left ventricle ejection fraction(LVEF)decreased to 45.3% from 64%. Therefore, we stopped TRS administration. Palpitation improved, and LVEF increased to 53% after 2 months. TRS was administered again; however, palpitation reoccurred and LVEF decreased to 44%. TRS administration was once again discontinued. However, according to the HERA trial report regarding patients with a history of anthracycline and radiation therapy, TRS administration could be resumed when LVEF is greater than 50%, but we should be more careful during readministration of TRS.

Objective: The clinical significance of preoperative chemotherapy, including trastuzumab for HER2-positive breast cancer, was examined based on hormone receptors(HR)to clarify future issues., Subjects: 104 HER2-positive breast cancer patients who completed preoperative chemotherapy and underwent surgery from May 2005 to August 2010. All patients received sequential treatment with taxane±trastuzumab for FEC(5-FU+epirubicin+cyclophosphamide)therapy, and from 2008 they received trastuzumab postoperatively for one year., Results: Concerning the histological effects, the rate of comprehensive pCR(CpCR)in the 104 patients(31 HR-negative administered trastuzumab, 15 HR-negative not administered trastuzumab, 28 HR-positive administered trastuzumab, 30 HR-positive not administered trastuzumab)was 65%, 47%, 21% and 23% for each group, respectively CpCR was a significant factor(p<0. 05)in prolonged distant disease-free survival(DDFS)in the HR-negative group. Distant metastasis occurred in 14 patients, namely, brain metastasis in 7 patients(4 HR-negative administered trastuzumab, 1 HR-negative not administered trastuzumab, 2 HR-positive administered trastuzumab). The therapeutic efficacy was pINV in 5 of these 7 patients(3HR-negative administered trastuzumab, 1 HR-negative not administered trastuzumab, 1 HR-positive administered trastuzumab), and 4 of those 5 patients received trastuzumab postoperatively., Discussion: The responsiveness to preoperative chemotherapy including trastuzumab for HER2-positive breast cancer differs between HR-positive and HR-negative. pINV patients seem to be at a high risk for brain metastasis regardless of HR, and it may be difficult to suppress its occurrence only with trastuzumab adjuvant therapy.

Unlabelled: It has been thought that there is a possibility that infusion speed generally affects the manifested frequency of infusion reaction and its strength. The infusion prescription time of trastuzumab should be over 90 minutes according to the package insert. In the infusion US, is possible over 30 minutes after the second time. We sought to evaluate the safety and tolerability of trastuzumab administered as a 30-minute infusion., Patients: Eighteen patients of HER2-positive breast cancer were treated, and their age ranged from 37 to 65 years old(median, 54 years old)., Method: PATIENTS were infused with 8 mg/kg of trastuzumab over 90 minutes and, if tolerated, all subsequent maintenance doses of 6 mg/kg are over 30 minutes., Result: The infusion times for 30 minutes were twice to 17 times(16 times the median). Mild infusion reactions were seen in 2 cases at the time of the initial prescription, but the infusion reaction was not judged from the prescription for 30 minutes. Mild eczema was admitted by 3 cases after prescription. No decline in cardiac function was seen., Conclusion: Our data strongly suggest that trastuzumab can be safely infused over 30 minutes for 6 mg/kg maintenance doses. However, it is thought that the number of cases will increase in future, and confirmation is necessary.

Unlabelled: As adjuvant chemotherapy for breast cancer, the addition of taxane to regimens containing anthracycline has been shown to be effective. However, in Japan, it is not probability yet as for safety. We examined the feasibility of FEC 100 followed by DOC 100 as adjuvant chemotherapy for breast cancer., Methods: Node-positive breast cancer patients or node-negative high-risk patients were eligible. The treatment completion rate and toxicity were evaluated in 3 courses of FEC 100 mg/m2 followed by 3 courses of DOC 100 mg/m2., Results: Twenty-one patients were registered and completion rate was 100%. The relative dose intensity (RDI) was 94.2% for FEC 100 and 97.8% for DOC 100. Grade 3 or higher neutropenia observed in 38% and febrile neutropenia developed in 14%. Non-hematological toxicities were slight., Conclusion: The regimen of FEC 100 followed by DOC 100 was safe in adjuvant chemotherapy for breast cancer in our country.

A case of occult breast cancer with pseudothrombocytopenia (PTCP) is reported. A 50-year-old woman was consulted with a left axillary tumor. Ductal carcinoma was found by the core needle biopsy, and no primary lesion was detected. Her preoperative platelet count, obtained from an ethylene diamine tetraacetic acid (EDTA) sampling bottle, was 3.1 x 10(4) per mL, but she had no history of bleeding problems. A heparinized blood sample showed a normal platelet count of 390 x 10(4) per mL. These findings suggested a diagnosis of occult breast cancer with EDTA-dependent PTCP, and level II axillary lymph node dissection was performed. She received adjuvant chemotherapy and radiotherapy, but she died 2 years and 5 months after the surgery because of lung and brain metastases. Awareness of the phenomenon and knowledge of the underlying physiological principles will enable surgeons to manage patients with EDTA-dependent PTCP appropriately.

Capecitabine + docetaxel combination therapy proves highly effective against the advanced or recurrent breast cancer. Therefore, it has been investigated as a first-line treatment for metastatic breast cancer. Hand-foot syndrome (HFS), a typical side effect of capecitabine, decreases the QOL of patients and sometimes prevents further medication using capecitabine. A 56-year-old woman who had liver, bone and local skin metastases two years after her left breast cancer operation, was treated with capecitabine + docetaxel combination therapy. Severe HFS disturbed the continuation of the therapy. Some other chemo-therapies were attempted after discontinuing the therapy; however, the metastases progressed. Finally, we tried to prevent HFS with vitamin B6 and started the capecitabine + docetaxel combination therapy. HFS was controlled completely. The liver tumor disappeared in MRI and CT images after 18 courses. In this case, vitamin B6 seemed to be effective to control HSF and allow continuation of capecitabine + docetaxel combination therapy.

The role and value of chemotherapy for soft tissue sarcomas remain unclear. Seventeen patients with pulmonary metastatic soft tissue sarcomas underwent treatment with chemotherapy, and the clinical efficacy and prognosis were studied. Six patients with synovial sarcomas, 4 with malignant fibrous histiocytomas, 4 with neurosarcomas, and the remaining 3 patients with leiomyosarcoma, extraskeletal osteosarcoma, and extraskeletal chondrosarcoma, were studied. Cases with small round cell sarcomas were excluded. The chemotherapy agents were ifosfamide in 10 cases, combination of ifosfamide and adriamycin in 5 cases, or cisplatin and adriamycin in 2 cases. Of the 17 patients, seven had partial responses radiographically and five had pulmonary metastases from synovial sarcoma. Eight patients underwent resection of pulmonary metastases following chemotherapy, and they were found to be residual tumor cells histologically. Twelve of the patients died of disease at 6-108 months (median, 30 months) from the time of the initial therapy, and five patients have survived from 1-53 months (median, 30 months). The absolute three-year survival rate, according to the Kaplan-Meier method, for all 17 patients was 39%. In the two cases with no change and progressive disease, all patients were dead within 2 years, while in the seven partial response cases, two patients were dead, four were alive with pulmonary metastases, and only one case was disease-free at this writing. The survival rate for patients with partial response was significantly higher than for patients with no response. Although the cure rate of pulmonary metastatic soft tissue sarcomas is still low, the combination of chemotherapy and surgery has been shown to result in prolonged survival.

From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).

In a recent 14-year period from December 1978 to December 1993, 180 patients with breast cancer were treated at the hospital, and out of these 180 patients, 38 patients (21.1%) who had a recurrent breast cancer were clinically evaluated. The first recurrence occurred in the local skin in 13 patients, regional lymph node in 1, bone in 13, lung in 4, liver in 4 and in other areas in 3. Histologically, the incidence of scirrhous carcinoma recurrence was higher than that of papillotubular carcinomas. There was no recurrence in mucinous carcinomas. The frequency of recurrence became higher in accordance with TNM classification, namely, 6.7% in Stage I, 23.7% in Stage II, 37.5% in Stage IIIa, and 47.1% in Stage IIIb cancers. An increasing tendency in the recurrence rate was also noted with an increase of tumor diameter or lymph node metastasis. Otherwise, there was no difference in cumulative survival after recurrence between TNM classification. There were no correlations between the estrogen receptor and incidence of recurrence or 5-year survival rate. The disease free interval (DFI) was less than 2 years in about 60% of the recurrent cases. DFI of bone metastasis was longer than for the other sites of recurrence. The survival rate increased according to prolongation of DFI. After through evaluation of these results, one should pay close attention to follow-up after mastectomy.

DNA ploidy pattern analyzed by cytofluorometry and p53 protein expression using immunohistochemical method were studied in 35 cases of esophageal cancer. p53 protein were positive in 19 cases (54%), and DNA aneuploidy pattern were detected in 26 cases (74%). There was no relationship between DNA ploidy pattern or p53 expression and clinico-pathological factors. DNA aneuploidy or p53 positive cases were significantly poor prognoses in five-year survival rate. DNA aneuploidy and p53 positive cases were worst in four groups. It is effective for evaluation of biological malignancy and detection of post operative schedules to study not only clinico-pathological factors but also DNA ploidy pattern and p53 expression in esophageal cancer.

The role of chemotherapy for soft tissue sarcoma with the exception of rhabdomyosarcoma remains controversial. Several randomized trials have suggested only doxorubicin (ADR) and ifosfamide produced a single-agent response rate above 20% in advanced sarcoma. As a combination chemotherapy, the doxorubicin-based combination, ADR + DTIC (ADIC) and CYVADIC, showed a higher response rate. Ifosfamide in addition to doxorubicin (Ifos + ADR or ADIC) appeared to have major activity with a higher complication rate. The role and value of adjuvant chemotherapy have not yet been established. Most randomized studies have suggested that no survival benefit was observed in the chemotherapy group relative to the control group. Further basic and clinical investigation is necessary to obtain a better prognosis in high-grade malignant soft tissue sarcoma.

A total of 64 courses of ifosfamide (IFM) treatments for sarcoma patients were evaluated for toxic effects. A dose of 100 ml of 1/2 diluted Maalox by normal saline was instilled into urinary bladder with clump of catheter for 15 min for uroprotection instead of Mesna that was not available in Japan at that time. Forty-six courses of ifosfamide treatment in 12-16 g/m2 doses with daily Maalox instillation resulted only one hemorrhagic cystitis, while 18 courses at a dose of 6-10 g/m2 of IFM without Maalox eventuated in 5 cases of hemorrhagic cystitis. Forty-six courses of ifosfamide treatment at a dose of 12-16 g/m2 (mean dose of 14.4 g/m2) for 5 to 6 day continuous infusion were evaluated also for myelosuppression, nephrotoxicity, neurotoxicity, and other toxicities. Myelosuppression was acceptable, although the absolute neutrophil count of the 80% course was below 500. No patient showed neurotoxicity characterized by confusion or somnolence. No course resulted in abnormal serum creatinine elevation, although two of 46 courses caused an abnormal decrease of creatinine clearance. One patient had arrhythmia that required medical treatment after 5 courses of IFM treatment.

UFT is given to the patients with digestive cancer from the time before operation to prevent intra- and post-operative cancer dissemination and metastases. UFT (400 mg/day in terms of tegafur) was given preoperatively for 1-6 days in 6 patients with gastric cancer and 13 with colorectal cancer. The interval between the last administration and the beginning of the operation was 3.9 +/- 1.5 hours (mean +/- SD). The concentrations of tegafur, 5-FU, and uracil in the blood collected at the time of tumor resection were 9.68, 0.017, and 0.08 microgram/ml, respectively. In the patients with gastric cancer 5-FU concentration was 5.5 times higher in the normal mucosa, 3.3 times in lymph nodes, and 10.7 times in the tumor tissues than in the blood. In colorectal cancer patients, also, the 5-FU concentration was 5.6, 8.3 and 20.8 times higher in the normal mucosa, lymph nodes, and the tumor tissue, respectively, than in the blood. The 5-FU concentration in gastric cancer and colorectal cancer tissues decreased with time after administration of UFT but remained above the effective concentration 1.5-7 hours after administration of 200 mg. The tissue concentrations of FT-207, uracil, and 5-FU were correlated with each other.

Long-term administration of PSK was made in 40 patients with urological cancer. Mean duration of the administration was 201, 358 and 243 days for the patients with bladder cancer, renal cancer and other urological cancers, respectively. The clinical evaluations were performed by the standard of Japan Society for Cancer Therapy and historical control study. In some cases, it seemed that the immunological therapy by PSK was a benefit to some degree. However, more accurate evaluation should be made by the matched control study.

Preoperative radiotherapy and systemic chemotherapy are effective for reducing the size of a tumor and rendering it resectable. The results achieved with systemic chemotherapy are ultimately reflected in improved survival. Moreover, limb-saving procedure in the treatment of osteosarcoma has become possible with rationality in carefully selected patients. Since 1975, 38 patients with osteosarcoma within an age range of 5 to 56 years, (average 17.9 years) have been treated by fast neutron radiotherapy, systemic chemotherapy and limb-salvage surgery. Twenty-two of these 38 patients underwent en bloc resection of the femur, eight resection of the proximal tibia and five resection of the proximal humerus. Only one of the 38 patients had evidence of local tumor recurrence and overall, 31 patients are currently alive without distant metastasis after 9 to 120 months follow-up. Preoperative fast neutron radiotherapy was employed and it was suggested that fast neutrons had a higher relative biological effectiveness and a greater therapeutic gain factor in comparison with X-rays. Fast neutron radiotherapy thus seems capable of playing a significant role in the treatment of osteosarcoma and is specifically useful for preservation of the affected limb.

Severe toxicity associated with high-dose methotrexate (HD-MTX) combined with citrovorum factor rescue (CR-Rescue) was evaluated in the 365 courses in 54 patients with osteosarcoma. Anaphylactoid reaction developed in 8 patients (14.8%), 8 courses (2.2%). The mean age was 14 years old. The total dose given was 85770mg in mean and 1840 mg per body weight (kg). The occurrence was proportional to the dose and the number of the course. Plasma MTX concentration remained under 10(-7) mol/l during the episode. Delayed clearance of MTX from plasma was treated with massive CF-Rescue in 10 patients (19%) (the mean age of 13.6), in 12 courses (3.3%), which was observed on an average at the 7th course when the total dose reached to 59530 mg, or 1390 mg per body weight (kg). Neurotoxicity was observed in only one patient (1.9%), one course (0.3%). Severe toxicity associated with HD-MTX therapy tended to occur according to dose escalation and the number of administration. To overcome severe toxicity careful observation of clinical symptoms and signs as well as adequate treatment of side effects without delay are of importance.

Clinical trials of UFT have been conducted on patients with far-advanced renal cell cancer with distant metastasis. All patients had evaluable lesions which had shown no change or progressive disease under prior therapy. Five of these cases had received Interferon as prior therapy. Thus far, the antitumor effects of the drug were evaluated in 8 cases according to the criteria proposed by the Koyama-Saito group. Partial response was obtained in 3 of 8 patients (37.5%). Two patients showed no change and three patients showed progressive disease UFT caused anemia and diarrhea in each of patients. To measure the 5-FU level in the tumor and normal kidney tissues UFT was administered at 600 mg per day on the day before radical nephrectomy in 2 patients, who had received embolization therapy of the renal artery prior to surgery. The 5-FU level was higher in tumor and normal kidney tissues than in serum, but there was no significant difference between tumor and normal kidney tissues. The embolization therapy of the renal artery may have been responsible for this result. UFT is one of the most useful drugs for the treatment of renal cell cancer.

The pre-operative radiotherapy and systemic chemotherapy is effective in reducing the size of tumor and making the tumor resectable. The results achieved with systemic chemotherapy are ultimately reflected in improved survival. Moreover, limb-saving procedure in the treatment of osteosarcoma has become possible with rationality in carefully selected patients. Sixty-seven patients with osteosarcoma within a range of 5 to 27 years of age were treated at Chiba Cancer Center Hospital in the recent 12 year-duration. Seventeen of 67 patients underwent en bloc resection for osteosarcoma of the femur, (12 patients) and the tibia (5 patients). No patients had evidence of local recurrence of the tumor and overall 15 patients are alive without distant metastasis after 9 to 120 months follow-up. Based on the effective chemotherapy schedule, the limb salvation in the treatment of osteosarcoma is most desirable if it is indicated without risk of decreased radicality of the treatment.

A total of 31 patients with malignant bone and soft tissue tumors were evaluated for toxic effects after receiving cisplatin (104 courses) at doses of 2.0-3.0 mg/kg with aggressive hydration. Nausea was common and in 86% of cisplatin courses severe vomiting was observed. Nephrotoxicity was observed in less than 10% of all courses but ototoxicity, especially tinnitis, developed in 5 of 6 patients whose total doses of cisplatin were over 500mg, and one of them showed hearing disorder in the upper frequency above 5,000 Hz. There were no other toxic effects such as severe myelosuppression, allergic reaction or peripheral neuropathy.