Nobuyuki Naka

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.

A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non-small cell lung cancer.

The split-course concurrent thoracic radiation therapy (TRT) and full-dose chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC) has produced promising results by comparison with the sequential approach. Instead of split-course radiation, we conducted a phase II study to investigate the feasibility of continuous concurrent TRT and chemotherapy. Twenty-two patients with unresectable NSCLC were enrolled onto a phase II study of continuous concurrent radiotherapy and chemotherapy. Treatment consisted of two courses of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29 and 36), and mitomycin (8 mg/m(2) on days 1 and 29). TRT began on day 2 at a dose of 60 Gy (2 Gy per fraction and 5 fractions per week for a total of 30 fractions). Of 22 patients assessable for response, none achieved a CR and 17 (77.3%) achieved a PR with an overall response rate of 77.3% (95% confidence interval, 54.6-92.2%). Grade 3 or 4 leukopenia was observed in 5/13 (81.8%) patients. Six patients (27.3%) experienced > or = grade 3 thrombocytopenia. Non-hematological toxicity was relatively mild. The overall median survival time was 19.0 months and the 1- and 2-year survival rates were 84.8 and 34.5%, respectively. It was possible to administer two courses of chemotherapy in 18 patients (81.8%) as planned. Nineteen (86.4%) of the 22 patients received the planned 60 Gy radiation. It seems to be difficult to administer the planned treatment without any interruption for the majority of patients. However, in the selected patients who completed the 60 Gy TRT, nearly half of the patients completed TRT without interruption. This combination regimen is considered to be feasible on condition that the stopping rule of the treatment is followed. We recommend administering radiotherapy continuously as far as possible.

The degree of exercise hypoxemia reflects pulmonary artery pressure during early exercise in chronic obstructive pulmonary disease patients

The causes of both exertional pulmonary hypertension and pulmonary hypertension in general in chronic obstructive pulmonary disease (COPD) remain to be elucidated. To further understand the pathophysiology in COPD patients, it may be important to recognize the existence of exertional pulmonary hypertension and to determine the severity of exertional hypoxemia. However, little is known about their relationship. To investigate whether the severity of exertional hypoxemia, as evaluated by the Δartery oxygen tension/Δoxygen consumption (PaO2‐slope) correlates with the mean pulmonary artery pressure (Ppa), cardiopulmonary exercise testing with haemodynamics was done in 10 patients with moderate to very severe COPD. The PaO2‐slope was significantly correlated with the mean Ppa from 25% to 40% of the maximum Watts (Wmax), and was most significant at 30% Wmax (r = −0·904, P<0·0001). In this phase, all parameters, except for the mean Ppa and the mixed venous oxygen tension, were not markedly changed from resting levels. At 30% Wmax, the mean Ppa (mean, 27 mmHg) with no or mild hypoxemia was also significantly correlated with the Δartery oxygen saturation/Δoxygen consumption (SpO2‐slope) (r = −0·789, P = 0·004). On stepwise multiple regression analysis, the PaO2‐slope was the most significant predictor of mean Ppa at 30% Wmax. In conclusion, the PaO2‐slope and the SpO2‐slope reflect Ppa during the early exercise phase. Thus, assessment of these parameters could be useful to evaluate the cardiopulmonary haemodynamic pathophysiology of COPD patients.