Single-agent paclitaxel as a 3-hour infusion.

This ongoing phase II trial of patients with inoperable stage IIIB-IV non-small cell lung cancer is seeking to determine the efficacy and toxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour infusion. The 58 patients now evaluable met standard eligibility requirements, including no prior chemotherapy. Paclitaxel 225 mg/m2 was delivered every 3 weeks for up to 10 courses, depending on patient response. All patients were evaluable for toxicity and 50 were evaluable for response. There were no complete responses, 12 patients had partial responses, 12 had progressive disease, and 26 had no change. The median time to response was 8.7 weeks; the median survival was 10 months. Leukopenia, when observed, was grade 1 or 2 in all but one case. Likewise, all nonhematologic effects were mild, with the exception of one case of grade 3 gastrointestinal toxicity. The 3-hour infusion schedule is more convenient, and the authors feel that the safety of the schedule is confirmed by these results. However, the efficacy of the shortened schedule, compared with a 24-hour infusion, remains to be proven.

Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. We investigated the efficacy and toxicity of a 3-hour paclitaxel infusion in a phase II trial in patients with inoperable stage IIIB or IV NSCLC. The 58 patients treated (41 men and 17 women) had a median age of 59 years (age range, 25 to 75) and a performance status of 0 through 2. Most patients (72.4%) had stage IV NSCLC. Paclitaxel 225 mg/m2 was infused over 3 hours every 3 weeks with standard prophylactic premedication. Of 50 patients evaluable for response, 12 (24%) had partial remission, 26 (52%) had no change, and 12 had disease progression (24%). Hematologic toxicities were mild: only one patient (2%) developed grade 3 or 4 neutropenia, while 29% had grade 1 or 2. Grade 1 or 2 polyneuropathy affected 56% of patients while only one (2%) experienced severe polyneuropathy. Similarly, grade 1 or 2 myalgia/arthralgia was observed in 63.2% of patients, but only 14.3% experienced grade 3 or 4. Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed.

Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer.

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone marrow imaging using 111In-citrate: 111In-kinetics in the pelvic region.

When bone marrow scintigraphy was performed using 111In-citrate, radioactivity was observed in the pudendal region. Subsequently, the kinetics of 111In in the pelvic region after intravenous administration of 111In-citrate for bone-marrow scanning in 14 patients was examined. On the first day, radioindium was found predominantly in the large pelvic blood vessels and in the pudendal region. In all male patients, the scrotal area was affected with both testes presumably delineated in two patients. In the female patients little radioindium was detected in the pudendal region, most probably in the vulva; distinct radioactivity was found in the pelvis although the ovaries could not be identified. In the following period the 111In uptake in the bone marrow increased considerably and reached its maximum usually 24 hr after the injection. Because a distinct radiation dose from 111In to the gonads cannot be excluded on the basis of our scintigraphic findings and the absorbed dose has not yet been estimated sufficiently, judgment should be used for the present if 111In-citrate is applied for bone marrow imaging.