Clinical Complete Responders Research Articles

Prolonged, alternating chemotherapy for extensive small cell lung cancer. A Southwest oncology Group study.

Etoposide may be schedule dependent in small cell lung cancer (SCLC), and some data suggest a benefit for increased dose intensity in this disease. This study attempted to optimize dose intensity using an outpatient program that included prolonged, oral etoposide administration. Cisplatin-etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV) were alternated at monthly intervals in patients with extensive SCLC. PE was given as cisplatin 50 mg/m2 on days 1 and 8 intravenously (i.v.) and etoposide 50 mg/m2/day for 14 days by mouth. CAV was administered as cyclophosphamide 60 mg/m2/day for 21 days orally, doxorubicin 20 mg/m2/week for three doses, and vincristine 2 mg i.v. on day 1 only. At the end of 4 months, responding patients received an additional course of PE alternating with CAV, and whole-brain irradiation (3000 cGy in 15 fractions) was delivered to clinical complete responders (CR). Among 61 eligible patients, 4 achieved CR, and 11 had a partial remission, by strict Southwest Oncology Group criteria. An additional 20 patients demonstrated greater than 50% tumor shrinkage on one disease assessment but did not have confirming measurements at all sites 4 weeks later. The overall response rate was 57%, including the latter group. The toxicity was primarily hematologic, with three treatment-related deaths from neutropenic infection (5%). Grade 4 neutropenia (< 500/microliters) occurred in nine patients (15%) and Grade 4 thrombocytopenia (< 25,000/microliters), in three (5%). Analysis of the delivered dose intensity (in milligrams per square meter per week) as a function of that which was planned revealed a mean of 93% for all courses. Although substitution of prolonged oral etoposide in PE and oral cyclophosphamide in CAV proved to be feasible, these results suggest no advantage over those from other reported series using these alternating regimens in which the agents are pulsed. Experience with alternating PE-CAV for extensive SCLC is reviewed.

5-fluorouracil (5-FU) and leucovorin in platinum-refractory advanced stage ovarian carcinoma

Twenty-nine patients with recurrent advanced stage ovarian cancer were treated with 5-fluorouracil (5-FU) and leucovorin by intravenous bolus on 5 consecutive days, repeated every 3 weeks. Twenty-one of these patients had experienced disease progression while receiving a cisplatin- or carboplatin-based regimen. There were 2 clinical complete responders and 1 partial responder to therapy (10% response rate; 95% confidence interval, 2 to 27%) and 11 individuals who experienced stable disease for periods ranging from 5 to 27 months. Of 204 cycles of therapy administered, 9 cycles were associated with hospitalization. These occurred in the more heavily pretreated members of the cohort. 5-FU and leucovorin appear to have activity in platinum-refractory ovarian cancer and form a well-tolerated regimen in most patients.

A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer.

Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.

CA-125 values predictive of clinical response during second-line chemotherapy for epithelial ovarian cancer.

Between November 1984 and January 1987, 19 patients with epithelial ovarian cancer were monitored with CA-125 values during second-line therapy. There was a statistically significant association between clinical response to therapy and CA-125 trend when trend was defined as a greater than or equal to 26% change in CA-125 from baseline value to last value prior to demonstration of clinical response (p = 0.0002). In 8 of 11 patients (73%), increasing CA-125 values were predictive of clinical progression during second-line therapy. In six of seven patients (86%), decreasing values predicted clinical regression. Three patients began second-line therapy with baseline values less than 35 U/ml. Two of these progressed during second-line therapy while the third progressed in follow-up. Two of four complete clinical responders completed second-line therapy with values less than 35 U/ml. Both progressed in follow-up with increasing CA-125 values. In this analysis, a 26% change in CA-125 values was a useful predictor of clinical response in patients receiving second-line therapy for epithelial ovarian cancer. Patients undergoing second-line chemotherapy with values less than 35 U/ml may still benefit from CA-125 monitoring.

Treatment of advanced ovarian cancer with cisplatin, adriamycin, and cyclophosphamide: effect of treatment and incidence of intracranial metastases.

A retrospective analysis of 42 patients with stage III, IV, or recurrent epithelial ovarian carcinoma treated with monthly cisplatin, Adriamycin, and cyclophosphamide (PAC) was made. Of 36 patients with measurable disease, 18 (50%) achieved a clinical complete response (CR) and 12 (33%) achieved a partial response (PR) for an objective response rate of 83%. Six stage III patients remained without measurable disease after surgery and postoperative PAC and are included in the survival data. The median survival of all patients was 22 months (10 months for nonresponders), with a median duration of response of 15 months (19+ months for clinical complete responders). Of 16 patients who underwent second-look laparotomy while in clinical CR, 8 were pathologically free of disease. Of these 8 surgically staged CRs, 2 have suffered CNS relapses, while the rest remain free of disease. One additional patient, who had been found to have only microscopic disease at the time of second-look surgery, subsequently relapsed in the CNS, for a total of 3 patients with CNS relapse. We conclude that PAC is an effective regimen, but that prolonged survival of these patients may put them at greater risk for CNS relapse.

Chemotherapy of advanced ovarian carcinoma: Initial experience using a platinum-based combination

Thirty-five previously untreated patients with FIGO Stage III or IV ovarian carcinoma were treated with cis-diamminedichloroplatinum (II), Adriamycin and cyclophosphamide (PACe). Following four or five cycles of PACe, patients were assessed clinically for response. Twenty-one (60%) of the patients attained a clinical complete remission (CCR), seven (20%) a partial remission, and seven (20%) did not respond. The median survival of all patients was 19 months, 6.4 months for partial and nonresponders, and 26.5 months for clinical complete responders. Six patients remain relapse-free for more than two years. Patients entering into the study during the second year underwent a second-look procedure if they attained a CCR. Ten patients in CCR were assessed for second look; two refused, and eight underwent a laparotomy. Three of eight were in complete remission after second look, and a fourth patient who had microscopic disease in one ovary was rendered free of disease by surgery. Subjective toxicity was marked due to severe nausea and vomiting. Renal toxicity was not troublesome and myelosuppression was moderate. Ototoxicity and peripheral neuropathies were seen in seven patients. PACe is a highly effective induction regime but randomized studies are required to show that improved survival will result from it's use.