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Survival of BRCA1 Breast and Ovarian Cancer Patients:
ASCO 1998: New data on lung cancer treatment

The ASCO meeting is one of the major events in the scientific world of oncology, a place where brand new results from clinical trials are presented. Out of the thousands of abstracts that have been submitted we selected some interesting data focusing on advanced breast cancer and NSCLC - two very common tumors that are still difficult to treat.

Promising data for cisplatin + navelbine

Advanced NSCLC (non small cell lung cancer) is still one of the most challenging tasks in cancer treatment. A new approach was investigated by a study group in San Antonio, Texas, comparing cisplatin alone with a combination of cisplatin + navelbine. According to Dr. J. J. Wozniak there were 415 evaluable patients included who had previously untreated stage IV (more than 90%) or stage IIIB NSCLC. The response rate was 12% in the cisplatin group compared with 26% in the patients who have been treated with the combination. A complete response could be achieved in only 2% of the patients in the cisplatin + navelbine arm. Progression of the disease occurred in 54% of the patients under treatment with cisplatin which is twice as high compared to the combination arm. The most frequent grade IV toxicity was granulocytopenia with 120 episodes reported in the combination treatment compared to 3 episodes under cisplatin alone. Looking at the survival rates also supports the conclusion that cisplatin + navelbine is superior to cisplatin alone. The corresponding survival rates after 1 and 2 years are 36% and 12% versus 20% and 6%.

Paclitaxel/platin combinations: alternative to standard therapy

Cisplatin + etoposide (CE) is one of the standard regimens for the treatment of advanced NSCLC. The new regimen of carboplatin + paclitaxel (CP) has become widely used in numerous centers due to reports from phase II studies. In order to compare these 2 treatment schedules a comparative study with 379 patients was carried out in the US. The treatment was administered every 3 weeks to a maximum of 10 courses provided that no unacceptable toxicity or disease progression was observed. Based on an intention to treat analysis there was a 14% response rate in the CE group while the treatment with CP resulted in a response rate of 22% of the patients, said Dr. C. R Belani, a difference that is not significant as well as the median survival time with 9,1 for CE and 7,7 for CR Future analyses will show if there is a difference with respect to survival rate.

Another trial carried out on an international basis further supports that paclitaxel in combination with cisplatin might be an alternative in the treatment of advanced NSCLC. In this study presented by Dr. U. Gatzemeier a high dose of cisplatin (100 mg/m2) was compared with paclitaxel (175 mg/m2) + cisplatin (80 mg/m2). Courses were repeated every 3 weeks to a median of 3 courses (1-9) in the cisplatin group and 5 courses (1-8) in the CP group. The response rate was significantly higher in the CP group (26% versus 17%) and the median time to progression also favored the PC regimen (4,1 versus 2,7 months). But concerning the median survival duration there was no significant difference between cisplatin (8,6 months) and CP (8,1 months). Taking into account the improved quality of life in the CP group this regimen is a promising alternative to standard therapy, said Dr. Gatzemeier.

Tirapazamine - a now approach for fighting cancer

Tirapazamine represents a new concept in cancer therapy which is based on the fact that hypoxia of tumor cells is a common phenomenon which is associated with resistance to chemotherapy. Tirapazamine acts by selectively damaging hypox:ic cells and providing synergistic effects with cisplatin. The clinical relevance of this concept was proven in a clinical trial (CATAPULT-1) in more than 400 patients with advanced NSCLC. Compared with cisplatin alone (75 mg/ml) the pretreatment with tirapazamine followed by cisplatin resulted in an improved response rate (27,5% versus 13,7%). Median survival duration was also higher in the TC group (34,6 versus 27,7 weeks) suggesting that this type of combination therapy is a very promising approach that deserves further investigation. The safety profile of the TC combination was also favorable. Toxicity was mild to moderate in most cases and did not include an increase in additional myelosuppression compared to cisplatin alone.

Gemcitabine + cisplatin: more effective than cisplatin alone

Cisplatin is one of the standard regimens for the treatment of NSCLC 'although the response rates are rather limited. A combination with gemcitabine seemed worth to be tested after having seen a considerable efficacy for this new substance in a monotherapy phase II trial, said Prof Sandler. Based on this data a randomized trial was initiated in which gemcitabine (1.000 mg/m') + cisplatin (100 mg/m2) was compared with cisplatin (100 mg/m') alone. A maximum of 6 cycles was administered unless progression of the disease led to a premature termination of the study. An interim analysis which included 309 out of more than 500 patients was presented by Dr. Sandler, who pointed out that two thirds of the patients presented with stage 4 disease. "The efficacy results are very impressing because compared to cisplatin alone the combination with gemcitabine resulted in a significant increase in the response rate (10% versus 32%)", said Dr. Sandler. The median duration of response was also increased in the gemcitabine + cisplatin group (6,9 versus 4,2 months) but without reaching statistical significance at this point of interim analysis. Looking the other way round on the median time to progression confirmed the superiority of the combination therapy showing a significant increase of progression free survival from 3,7 to 5,8 months. But more important, the analysis of the final data as far as available up to now yielded a significant increase in median survival time (9,1 versus 7,6 months) and an improved one year survival probability for the combination arm (39% versus 28%). Although the bone marrow toxicity was more pronounced in the gemcitabine + cisplatin group this regimen looks very promising, concluded Dr. Sandler

Gemcitabine + cisplatin: superior to MIC regimen

The favorable effects of gemcitabine + cisplatin in patients with advanced NSCLC was confirmed by an Italian study group which undertook a comparison against the MIC regimen (mitomycin, ifosfamide, cisplatin) on more than 300 patients 80% of whom having stage IV disease. According to the presenter of the study, Dr. Crino, the response rate of 38% was quite encouraging for the combination therapy with gemcitabine + cisplatin yielding a significant difference in comparison to the MIC group (26%). What is another important feature of this study results from the clinicians' view is the equal efficacy of gemcitabine + cisplatin in patients with stage III and stage IV disease (41% versus 37%) whereas the MIC regimen worked considerable poorer in stage IV (23%) than in stage III patients (37%). As to the safety aspect Dr. Scagliotti pointed out that there was initially a higher bone marrow toxicity in the gemcitabine + cisplatin group that diminished with time due to dose adaptation. Therefore the evaluation on day 29 did not reveal a relevant difference in hematological side effects. With respect to other side effects there was a significant advantage for gemcitabine + cisplatin when looking at the incidence of hair loss (12% versus 39%) and nausea/vomiting (18% versus 23%).

Gemcitabine + cisplatin: a major advance

Another study with gemcitabine + cisplatin in patients with NSCLC (locally advanced or metastatic disease) was presented by Dr. R. Rosell. In this trial the combination of etoposide + cisplatin served as a control group. A total of 135 patients was recruited including 50% with stage 11113 and stage IV disease respectively. Like in the other 2 studies mentioned before gemcitabine + cisplatin proved to be a very efficacious regimen yielding a response rate of 41% compared to 22% in the etoposide + cisplatin group, a difference that is statistically significant. Concerning the median duration of response a trend in favor of gemcitabine + cisplatin was observed (8,4 versus 6,1 months). The median time to progression of the disease was significantly prolonged in the gemcitabine + cisplatin group (6,9 versus 4,3 months) and furthermore an increased probability of 1 year survival could be achieved (32% versus 26%). As to toxicity there were no relevant differences between the 2 groups reported, leading Dr. Rosell to the conclusion that gemcitabine in combination with cisplatin represents a major advance in the treatment of patients with NSCLC.

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