This Phase II study was conducted to evaluate efficacy and safety of gemcitabine monotherapy in anthracycline and taxane pre-treated Japanese metastatic breast cancer patients.
At Step 1, twelve patients were divided into two groups of six patients each and the dose-limiting toxicity was evaluated at gemcitabine 1000 and 1250 mg/m2 to determine the dose for Step 2. At Step 2, an additional 56 patients were assessed for efficacy and safety of gemcitabine monotherapy. Patients were treated with gemcitabine on days 1 and 8 of a 21-day cycle and explored incidence of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, overall response rate (RR), time to progression disease and overall survival time.
Gemcitabine 1250 mg/m2 was determined as the dose for Step 2. Adverse events reported in this study were similar in type, frequency and toxicity grades as seen in other tumor types. Of the 62 patients at 1250 mg/m2, 1 complete response (1.6%), 4 partial response (6.5%) and 20 stable disease (32.3%) were achieved, yielding an RR of 8.1% (95% CI: 2.7%, 17.8%). Median time to progression was 92.0 days (range: 29–651 days). The median survival time was 17.8 months (95% CI: 14.9 months to incalculable).
Gemcitabine at 1250 mg/m2 on days 1 and 8 of a 21-day cycle was tolerable and can be a salvage treatment option for Japanese metastatic breast cancer patients previously treated with anthracyclines and taxanes.
To identify any gender differences in the outcomes of concurrent platinum-based chemotherapy and thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC).
A comparative retrospective review of the clinical characteristics and treatment outcomes between female and male NSCLC patients receiving chemoradiotherapy.
Of a total of 204 patients, 44 (22%) were females and 160 (78%) were males. There was no difference in age, body weight loss, performance status or disease stage between the sexes, whereas never-smokers and adenocarcinoma were more common in female patients (55% vs. 3%, P < 0.001, and 73% vs. 55%, P = 0.034, respectively). Full cycles of chemotherapy and radiotherapy at a total dose of 60 Gy were administered to ~70% and >80% of the patients, respectively, of both sexes. Grade 3–4 neutropenia was observed in 64% of the female patients and 63% of the male patients. Severe esophagitis was encountered in <10% of the patients, irrespective of the sex. The response rate was higher in the female than in the male patients (93% vs. 79%, P = 0.028), but the median progression-free survival did not differ between the sexes. The median survival time in the female and male patients was 22.3 and 24.3 months, respectively (P = 0.64).
This study failed to show any gender differences in the survival or toxicity among patients treated by concurrent chemoradiotherapy. These results contrast with the better survival in female patients undergoing surgery for localized disease or chemotherapy for metastatic disease.
A multicenter trial was conducted to evaluate the efficacy and safety of paclitaxel every 2 weeks in patients with advanced or recurrent gastric cancer who had previously received fluoropyrimidine-based chemotherapy.
The subjects were patients with gastric cancer who had disease progression or recurrence while receiving fluoropyrimidine-based chemotherapy. All patients had adequate major organ functions with an Eastern Cooperative Oncology Group performance status (PS) of 0–2. Paclitaxel 140 mg/m2 was administered intravenously on days 1 and 15 of a 4-week cycle. The primary endpoint was the response rate. Secondary endpoints were progression-free survival (PFS), overall survival and safety.
Response was assessable in 40 of 41 enrolled patients. Their median age was 63 (range: 48–77) years, and PS was 0 in 22 patients, 1 in 13 and 2 in 5. Previous treatment included S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) monotherapy in 32 patients and S-1-based combination therapy in 5. The median number of administered courses of paclitaxel was 3.5 (1–14). The response rate was 17.5% (95% confidence interval: 7.3–32.8%, partial response: 7, stable disease: 21, progressive disease: 10 and not evaluable: 2). The disease control rate was 70.0%, the median PFS was 111 days and the median overall survival was 254 days. Major adverse events of Grade 3 or 4 were neutropenia (27.5%), anemia (12.5%), diarrhea (2.5%) and sensory neuropathy (2.5%).
Biweekly paclitaxel seemed to be one of the useful chemotherapies after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer.
We conducted a Phase II trial to investigate the efficacy of combined therapy with meloxicam, a cyclooxygenase-2 inhibitor and natural interferon (IFN)- in renal cell carcinoma patients with distant metastasis.
The subjects of this study were patients with untreated renal cell carcinoma who were diagnosed from the results of imaging or pathological studies and who had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients could be enrolled in the study irrespective of whether nephrectomy had been performed. Treatment involved the subcutaneous injection of natural IFN- at 3 x 106 or 5 x 106 U three times weekly plus oral administration of meloxicam at 10 mg once daily.
A total of 43 patients were enrolled in the present study, included 11 patients without nephrectomy, 23 patients with a high C-reactive protein (CRP) level and 23 patients with extrapulmonary metastasis. Four patients of complete response and 12 patients of partial response were confirmed, given an overall response rate of 37.2% (95% confidence interval, 23.0–53.3%). Stable disease for 6 months or longer was also obtained in 14 patients. The median time to progression was 14 months. Adverse events (AEs) observed were mainly flu-like symptoms due to cytokine. Although the Grade 3 or 4 AEs were fatigue, hepatic dysfunction, arthritis and gastric ulcer, all but one (gastric ulcer) were immediately improved by discontinuation of this combined therapy.
The combination of meloxicam and natural IFN- is considered to be an active regimen with tolerable toxicities as a first-line treatment of metastatic renal cell carcinoma.
Detection of prostate cancer needs a biopsy of the prostate. Suspecting cancer from an increase in prostate-specific antigen (PSA) has a high negative rate at an initial prostate biopsy. Cases with negative initial biopsy may be the candidates of subsequent biopsy. For lowering unnecessary repeat biopsy, the use of predictive factors before a repeat biopsy is applied for indication.
Seventy-seven cases with negative initial prostate biopsy received a repeat biopsy and factors for the detection of cancer were examined.
PSA doubling time distinguished a part of cancer cases. Its sensitivity of 30, 50 and 70 months was 36.6%, 30.4% and 10%, respectively. Cancer case did not show PSA doubling time of >100 months in general. Values of PSA transition zone density, %Free/total PSA and PSA velocity were similar between cancer and no cancer cases.
PSA doubling time was one of the predictive factors for the detection of prostate cancer and was valuable for avoiding unnecessary repeat biopsy in some cases.
We evaluated health-related quality of life (HRQOL) in patients with localized prostate cancer who underwent intensity-modulated radiation therapy (IMRT) or three-field conformal radiotherapy (3DCRT).
A total of 97 patients underwent 3DCRT and 36 underwent IMRT for localized prostate cancer between 2002 and 2004. We measured the general and disease-specific HRQOL with the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles Prostate Cancer Index, respectively.
There were no significant differences in the pre-operative characteristics of the two groups. The patients in the 3DCRT group were more likely to receive hormonal therapy compared with the IMRT group before and after radiation therapy (P < 0.001 and P = 0.011, respectively). With regard to general HRQOL domains, both the 3DCRT and IMRT group scores showed no significant difference between baseline and any of the observation periods. At 60 months after treatment, the 3DCRT group had significantly worse bowel function and bother scores than baseline (both P < 0.001). On the other hand, there were no significant differences between the baseline and any of the post-treatment time periods in the IMRT group. In the 3DCRT group, sexual function remained substantially lower than the baseline level (P = 0.023). The IMRT group tended to show a decrease in sexual function, which was not statistically significant (P = 0.11).
IMRT can provide the possibility to deliver a high irradiation dose to the prostate with satisfactory functional outcomes for long-term periods.
Reconstruction for osteosarcoma around the knee after wide resection faces the challenge of great bone defect and future limb length discrepancy in the skeletally immature patients. Modern prosthetic reconstruction may provide good results, but the longevity may be of concern and may not be affordable in certain communities. Allograft knee arthrodesis still has its role in light of bone stock preservation and cost-effectiveness.
We developed the innovative trident fixation technique utilizing three Steinmann pins to minimize limb length inequality without jeopardizing knee fusion stability. Twelve patients were enrolled. The mean age was 11.5 (10–13) years. Two had high-grade osteosarcoma in proximal tibia and others in distal femur.
Two patients died of oncological disease. The median follow-up of the disease-free 10 patients was 47 (41–60) months. All allograft-host bone junctions healed uneventfully without major complications except one allograft fracture. The average limb length discrepancy was 1.45 (1.0–2.1) cm at latest follow-up.
This straightforward technique was successful in knee arthrodesis with minimized limb length inequality. Accordingly, in light of bone stock preservation and longevity for the young children, it may be a surgical alternative for malignant bone tumors around the knee.