To test whether alternating chemotherapy is a favorable treatment modality in small-cell lung cancer (SCLC), 334 patients were randomized to receive either fixed cyclic-alternating treatment with ifosfamide/etoposide (IE), cyclophosphamide, doxorubicin, and vincristine (CAV), or response-oriented treatment with IE therapy up to maximal response and subsequently an immediate switch to CAV. In both arms, six cycles were given in 3-week intervals. After chemotherapy, patients with limited-stage disease received chest irradiation with 45 Gy. Prophylactic cranial irradiation with 30 Gy was applied to all complete responders. No maintenance therapy was given to patients with complete response. Minimum follow-up was 2 years. Of 321 assessable patients, the overall response rate was 70% for cyclic alternating and 77% for response-oriented treatment. Complete remission (CR) rates were 26% versus 26%. The median survival times were 9.7 months for cyclic-alternating versus 10.7 months for response-oriented treatment; the 2-year survival rates were 11% versus 9%. In limited-stage disease (LD) patients, there was a median survival of 12.5 months versus 12.3 months and a 2-year survival rate of 21% versus 18%. In extensive-stage disease (ED) patients, median survival was 8.5 versus 9.1 months, and the 2-year survival rate 3% versus 4%. From these results, we conclude that the cyclic-alternating treatment according to the hypothesis of Goldie et al has no advantage in comparison to a sequential treatment strategy with an immediate switch to a second-line protocol at the time no further response to first-line therapy is seen. Our major aim in the treatment of SCLC is to administer an active regimen at any time during the course of treatment regardless of whether sequential or alternating therapy is used.

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.

11 patients (age 36-60 years) with breast cancer and CT-scan documented brain metastases (BM) were treated with hormonochemotherapy: 5-fluorouracil 500 mg/m2 i.v. day 1 + 8, adriamycin 50 mg/m2 i.v. day 1, cyclophosphamide 500 mg/m2 i.v. day 1-q4 weeks (FAC) and tamoxifen (TXF) 20 mg/day per os. Ovarectomy was carried out in 3 praemenopausal patients. In 3 cases single BM were surgically resected (2 subtotal, 1 total). One patient was shunted due to a hydrocephalus occlusus. Complete response (CR), i.e. normalization of CT-scan and disappearance of CNS related symptoms, was achieved in 9 out of 11 patients. One patient with partial remission (PR) and another with progressive disease died 6 and 5 months after diagnosis of BM. The median duration of remissions of all patients was 12 (5-43) months. The median survival time from diagnosis of BM was 15 (5-44) months and from mastectomy 46 (26-142) months. The cumulative probability of surviving was 63% one year after diagnosis of BM. One relapsing patient achieved a second CR, another a PR by whole brain irradiation. 4 patients survived more than 18 months from the diagnosis of BM. It appears that chemo-hormonotherapy provides a rational approach to palliation in breast cancer patients with BM in prolonging the survival.

Forty-six patients with non-small cell lung cancer were treated with a combination of cis-platinum 90 mg/m2 i.v., day 1 and VP 16-213 100 mg/m2 i.v. on days 1, 3 and 5. The overall remission rate was 22% (10 out of 46 patients) with a median remission duration of 7 months. Squamous cell and large cell undifferentiated carcinomas responded to the chemotherapy with a remission rate of 27% (7 out of 26 patients) and 22% (3 out of 13 patients). Seven patients with adeno-carcinoma did not respond to chemotherapy. The overall survival was 7 months (1-27+). The survival time for patients entering remission was 11.5 months (7-27+), for those with stable disease 8.5 months (3-27+), and for patients with progressive disease 5 months (1-9). Performance status of less than 80%, a weight loss of more than 10.0 kg in the last three months before starting treatment and a "major" atelectasis (collapse of at least one superior or inferior lobe) adversely influenced prognosis. Only 1 out of 31 patients with one or more poor prognostic factors came into remission. In contrast, 9 out of 15 patients (60%) without poor prognostic factors had a remission. Stage, limited versus extensive disease, and age did not affect the results. Hematologic and renal toxicity of the combination were mild, but poor subjective tolerance (nausea, vomiting, loss of appetite) was prominent.

Die Kombination von VP 16–213, 100 mg/m2 Tag 1, 3 und 5 und Cis-Platin 90 mg/m2 Tag 1 wurde bei 46 Patienten zur Behandlung inoperabler nichtkleinzelliger Bronchialkarzinome eingesetzt. Die Remissionsrate betrug 22% (1 komplette und 9 partielle Remissionen). Plattenepithelkarzinome (7 von 26 Patienten, 27%) und großzellige undifferenzierte Karzinome (3 von 13 Patienten, 23%) sprachen auf die Therapie an; dagegen wurde bei 7 Patienten mit Adenokarzinom keine Remission induziert. Die mediane Remissionsdauer betrug 7 Monate (4–27+). Die medianen Überlebenszeiten waren für Patienten mit Remission 11,5, für Patienten mit unveränderten Tumorparametern 8,5 und für Patienten mit progredientem Tumor 5 Monate. Als prognostisch ungünstig erwiesen sich ein Karnofsky-Index unter 80 %, ein Gewichtsverlust von mehr als 10,0 kg in den letzten 3 Monaten vor Therapiebeginn und das Vorliegen einer Atelektase eines Lungenober- oder Lungenunterlappens. Von 31 Patienten mit einem oder mehr prognostisch ungünstigen Faktoren sprach nur einer auf die Therapie an. Dagegen wurden 9 Remissionen bei den 15 Patienten ohne ungünstige prognostische Faktoren induziert (Remissionsrate 60%). Tumorausdehnung und Alter hatten keinen Einfluß auf die Remissionsrate. Bei relativ geringer objektiver Toxizität waren die therapieinduzierten subjektiven Beschwerden erheblich. Es bestand ein deutliches Mißverhältnis zwischen dem Therapieergebnis und der subjektiven Toxizität.