Pemetrexed in combination with cisplatin (Pem/Cis) is used globally for the treatment of malignant pleural mesothelioma (MPM). This Phase I/II study was conducted to determine the recommended dose (RD) (Phase I) of Pem/Cis, and evaluate the efficacy and safety (Phase II) in Japanese MPM patients.
Key eligibility criteria were histologic diagnosis of MPM incurable by surgery, no prior chemotherapy, and a performance status 0–1. Under full vitamin supplementation, pemetrexed was intravenously administered on Day 1 of a 21-day cycle, followed by cisplatin. A cohort of six patients, starting from pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 (Level 1), were studied in the dose-escalation Phase I (Step 1). The RD determined in Step 1 was carried forward into Phase II (Step 2). Planned number of patients treated with Pem/Cis was 18–38.
In Step 1, 13 patients were enrolled: seven in Level 1 and six in Level –1 (pemetrexed 500 mg/m2, cisplatin 60 mg/m2). Two of six evaluable patients had dose-limiting toxicities (pneumonitis and neutropenia) in Level 1, establishing Level 1 as the RD. In Step 2, 12 patients were enrolled, for a total of 19 patients treated at the RD. Seven patients achieved a partial response among these patients, for a response rate of 36.8% (95% confidence interval: 16.3–61.6); overall survival was 7.3 months. One drug-related death occurred due to worsening of a pre-existing pneumonia. Common grade 3/4 toxicities were neutropenia and decreased-hemoglobin.
The Pem/Cis combination provides promising activity and an acceptable safety profile for chemonaive Japanese MPM patients with the same recommend dosage and schedule used in rest of the world.
The purpose of this study was to assess the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for lymph node (LN) metastasis of colorectal cancer.
FDG-PET/CT was used to preoperatively evaluate 88 patients with colorectal cancer. In this study, LN sites were divided into proximal and distant according to their distance from the primary tumor. The FDG-PET/CT images were evaluated by three criteria; nodal diameter, abnormal uptake and maximum standardized uptake value (SUV). We compared the diagnostic ability of these methods for LN metastasis at proximal and distant sites.
The mean SUV of the malignant LNs was significantly higher than that of the benign LNs. The sensitivity, specificity and accuracy of diagnosis by abnormal uptake were 28.6, 92.9 and 75.0%, those by nodal diameter using cutoff value of 10 mm were 30.6, 95.3 and 74.4% and those by SUV using cutoff value of 1.5 were 53.1, 90.6 and 80.1%, respectively. The sensitivity, specificity and accuracy of diagnosis based on optimal SUV were 51.2, 85.1 and 69.3% in the proximal site and 62.5, 92.5 and 89.7%, respectively, in the distant site.
FDG-PET/CT is useful for preoperative diagnosis of distant LN metastases of colorectal cancers.
To evaluate acute morbidity, radiation dermatitis and pneumonitis, of Japanese patients treated with whole breast hypofractionated radiotherapy (RT) after breast-conserving surgery (BCS), compared to conventional RT.
Japanese patients who received whole breast RT after BCS between October 2003 and September 2006 were retrospectively reviewed. Patients who had selected the conventional or hypofractionated schedule received whole breast irradiation of 50 Gy in 25 fractions plus boost or 40 Gy in 16 fractions plus boost. Radiation dermatitis and symptomatic pneumonitis were graded according to the Common Terminology Criteria for Adverse Events version 3.0.
Of 443 consecutive patients, 377 (85%) received the conventional schedule and 66 (15%) received the hypofractionated schedule. Of patients treated with the conventional schedule, Grade 0, 1, 2 and 3 radiation dermatitis were observed in 16 (4%), 278 (74%), 77 (20%) and 6 (2%), respectively. Of patients treated with the hypofractionated schedule, Grade 0, 1, 2 and 3 dermatitis were observed in 11 (17%), 49 (74%), 5 (8%) and 1 (1%), respectively. Grade 2–3 dermatitis by the hypofractionated schedule (9%) was observed less frequently than that by the conventional schedule (22%) (chi-square test; P = 0.016). Moreover, of patients treated with the conventional schedule, 4 (1%) had Grade 2 radiation pneumonitis. No patient treated with the hypofractionated schedule had symptomatic pneumonitis.
Radiation dermatitis and pneumonitis in Japanese patients treated with the hypofractionated schedule is acceptable. Especially, radiation dermatitis by the hypofractionated schedule is milder than that by the conventional schedule.
Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Western patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with prednisolone in Japanese patients with HRPC.
Patients aged 50–74 years with measurable metastatic HRPC were included in this non-comparative Phase II study. Treatment consisted of docetaxel 70 mg/m2 once every 3 weeks plus prednisolone 5 mg twice daily, for a maximum of 10 cycles. The primary endpoint was overall tumor response rate, assessed by Response Evaluation Criteria in Solid Tumors; secondary endpoints included prostate-specific antigen (PSA) response and toxicity.
A total of 43 patients were evaluable for efficacy and toxicity. The response rate was 44.2% (90% CI, 31.2–57.8%), with partial responses in 19/43 patients. The median duration of response was 19.3 weeks. PSA responses were recorded in 44.4% of patients (95% CI, 27.9–61.9%). The most common non-hematological adverse events (of any grade) possibly related to treatment were alopecia (88.4%), anorexia (65.1%) and fatigue (53.5%). Grade 3/4 leukopenia and neutropenia occurred in 81.4 and 93.0% of patients, respectively; however, the grade 3/4 rates of febrile neutropenia (16.3%) and infection without fever (14.0%) were lower.
The combination of docetaxel and prednisolone was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in Western patients.
Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found.
One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy.
The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 ± 4.8% [95% confidence intervals (CI)] and 30.2 ± 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20–30 Gy WB, and 500 mg/m2 of MTX dose appeared important determinants of OS.
A modest dose of MTX (500 mg/m2) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.
The aim of this study was to examine the appropriateness of chemotherapy and care in Korean cancer patients near the end-of-life.
We designed a retrospective cohort composed of patients diagnosed as having metastatic cancer and who received palliative chemotherapy at Seoul National University Hospital in 2002. Two hundred and ninety-eight patients who died of cancer were evaluated in terms of the appropriateness of the cancer-care they received, including chemotherapy.
Median duration of chemotherapy was 6.02 months compared with 8.67 months for median overall survival. The median period between last chemotherapy and death was 2.02 months. Of the 298 patients, 50.3% received chemotherapy during the last 2 months of life. Furthermore, 17 patients (5.7%) died within 2 weeks after receiving chemotherapy. The proportion who visited an emergency room (ER) more than once during the last months of life was 33.6%, and the average number of ER visits after a diagnosis of cancer was 1.72. Only 9.1% of patients were referred to a hospice consultation service and only 11.7% of patients agreed with written DNR.
Among patients who died of cancer, significant proportions were found to have received chemotherapy up to the end-of-life and to have visited ERs. Hospice referrals and discussions about DNR were not conducted well during the end-of-life period in Korea.