Vinorelbine Plus Chemo Promising in Advanced Disease

April 1, 1995

SAN ANTONIO--Three different regimens of vinorelbine tartrate (Navelbine) combined with established chemotherapeutic agents led to significant responses in up to 60% of patients with advanced or metastatic breast cancer, including previously treated patients.

SAN ANTONIO--Three different regimens of vinorelbine tartrate(Navelbine) combined with established chemotherapeutic agentsled to significant responses in up to 60% of patients with advancedor metastatic breast cancer, including previously treated patients.

In the largest of the three studies, 35 (56.4%) of 62 patientswith metastatic breast cancer responded to the combination ofvinorelbine and doxorubicin as first-line chemotherapy. Sevenpatients had complete responses, and 28 had partial responses;an additional 16 patients remained stable, New York Universityoncologist Howard Hochster reported at a general session of theSan Antonio Breast Cancer Symposium.

The dosing regimen consisted of 50 mg/m² of doxorubicin onday 1, and 25 mg/m² of vinorelbine on days 1 and 8. The regimenwas repeated every 3 weeks for eight cycles, after which patientscontinued weekly vinorelbine until progression. The patients completeda median of six cycles, and 30% completed eight cycles, said Dr.Hochster, assistant professor of medical oncology/hematology.

The doxorubicin dose was reduced to 40 mg/m² for patientswhose ANC was between 1,000 and 2,000, or whose platelet countwas 75,000 to 100,000. If the ANC fell below 1,000, or plateletsbelow 75,000, the day 1 doses of doxorubicin and vinorelbine weredelayed for a week. The day 8 vinorelbine dose was delayed 1 weekfor grade 4 neutropenia, or if platelets fell below 75,000.

One-year survival for the cohort was 75%, and 44% of the patientshave died. Median survival was 94 weeks, and median time to progressionwas 34 weeks.

Grade 4 granulocytopenia occurred in 87% of the patients but,in most cases, did not require intervention, Dr. Hochster said.Dose modifications mitigated problems with further episodes ofgranulocytopenia, which occurred in only 30% of all chemotherapycycles. Eighteen patients required hospitalization for febrileneutropenia.

Thrombocytopenia, nausea, and vomiting were not significant problems.Three cases of grade 3 cardiotoxicity occurred, and one patientdied of heart failure.

A total of 148 patients in various studies have been treated withthe doxorubicin-vinorelbine combination regimen, Dr. Hochstersaid. The overall response rate has been 68%, including completeresponses in 18%.

"Because of its high activity and acceptability, this combinationhas significant potential as adjuvant therapy," Dr. Hochsterconcluded. "Granulocytopenia has been the major toxicityin all studies, and about a quarter of patients have had febrileneutropenia. With appropriate dose modification, I think we canlower the incidence of grade 4 granulocytopenia considerably."

Italian Study

The combination of vinorelbine and cisplatin (Platinol) producedsignificant responses in 16 of 26 patients with metastatic breastcancer enrolled in an Italian trial. One patient had a completeresponse. Fifteen patients previously had been treated with oneor more chemotherapy regimens.

The study regimen consisted of 80 g/m² to 100 mg/m²of cisplatin on day 1, and 20 mg/m2 to 25 mg/m² of vinorelbineon days 1 and 15. The regimen was repeated every 4 weeks, saidGiorgio Mustacchi, MD, director of clinical oncology, the Universityof Trieste Cancer Center.

The median time to progression was 22 weeks in previously treatedpatients, and median survival was 35 weeks. Seven of 11 untreatedpatients had significant responses at a median follow-up of 30weeks.

Dr. Mustacchi described the toxicity as acceptable. White bloodcount fell below 4,000 in 87 of 116 cycles. Anemia (hemoglobinless than 10 g/dL) occurred in 13 patients, grade 3 asthenia infour.

"This combination regimen is active in heavily pretreatedpatients and as first-line therapy for metastatic disease,"Dr. Mustacchi said in his poster presentation. "The combinationis well tolerated and easy to administer in the outpatient setting."

Ochsner Cancer Institute Study

Vinorelbine combined with mitomycin (Mutamycin) produced significantresponses (one complete) in seven of 21 breast cancer patients(one unevaluable) who had metastatic disease or who had relapsedafter adjuvant chemotherapy. All but one of the patients had beenpreviously treated, 17 with anthracyclines, said John T. Cole,MD, of the Ochsner Cancer Institute, New Orleans. Four of nineanthracycline-resistant patients had objective responses.

The median duration of response was 20 weeks. Sites of responsewere the liver (3), lung (3), and bone (1).

The chemotherapy regimen consisted of 8 mg/m² of mitomycinon days 1 and 29, and then every 6 weeks. Vinorelbine was givenat a dose of 30 mg/m² weekly for 4 weeks, with half dosesgiven on days 8 and 22.

Grade 3 or 4 leukopenia occurred in six patients, and one patienteach had grade 3 thrombocytopenia and anemia. Among nonhematologictoxicities, five patients had grade 3 or 4 nausea, and four hadgrade 3 vomiting and back pain.